Prausnitz is the J. Erskine Love Jr. Chair of the School of Chemical and Biomolecular Engineering (ChBE) and director of Georgia Tech’s Center for Drug Design, Development and Delivery. He’s also the only Georgia Tech faculty member recognized as both a Regents’ Professor and Regents’ Entrepreneur, the highest academic titles awarded by the University System of Georgia Board of Regents. He joins 105 new NAE members in the 2023 class along with 18 new international members.

Read the full story on the College of Engineering website.

The possible treatment, which could become the first non-drug, non-surgical, long-acting therapy for glaucoma, uses the injection of a natural and biodegradable material to create a viscous hydrogel — a water-absorbing crosslinked polymer structure — that opens an alternate pathway for excess fluid to leave the eye. 

“The holy grail for glaucoma is an efficient way to lower the pressure that doesn’t rely on the patient putting drops in their eyes every day, doesn’t require a complicated surgery, has minimal side effects, and has a good safety profile,” said Ross Ethier, professor and Georgia Research Alliance Lawrence L. Gellerstedt Jr. Eminent Scholar in Bioengineering in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “I am excited about this technique, which could be a game-changer for the treatment of glaucoma.”

The research, which was supported by the National Eye Institute and the Georgia Research Alliance, was published Dec. 7 in the journal Advanced Science. The research was conducted in animals, and shows that the approach significantly lowered the intraocular pressure.

As many as 75 million people worldwide have glaucoma, which is the leading cause of irreversible blindness. Glaucoma damage is caused by excess pressure in the eye that injures the optic nerve. Current treatments attempt to reduce this intraocular pressure through the daily application of eyedrops, or through surgery or implantation of medical devices, but these treatments are often unsuccessful.

To provide an alternative, Ethier teamed up with Mark Prausnitz, professor and J. Erskine Love Jr. Chair in the School of Chemical and Biomolecular Engineering at Georgia Tech, to use a tiny hollow needle to inject a polymer preparation into a structure just below the surface of the eye called the suprachoroidal space (SCS). Inside the eye, the material chemically crosslinks to form the hydrogel, which holds open a channel in the SCS that allows aqueous humor from within the eye to drain out of the eye through the alternative pathway.

There are normally two pathways for the aqueous humor fluid to leave the eye. The dominant path is through a structure known as the trabecular meshwork, which is located at the front of the eye. The lesser pathway is through the SCS, which normally has only a very small gap. In glaucoma, the dominant pathway is blocked, so to lessen pressure, treatments are created to open the lesser pathway enough to let the aqueous humor flow out.

In this research, the hydrogel props open the SCS path. A hollow microneedle less than a millimeter long is used to inject a droplet (about 50 microliters) of the hydrogel-precursor material. That gel structure can keep the SCS pathway open for a period of months.

“We inject a viscous material and keep it at the site of the injection at the interface between the back of the eye and the front of the eye where the suprachoroidal space begins,” Prausnitz said. “By opening up that space, we tap a pathway that would not otherwise be utilized efficiently to remove liquid from the eye.”

The injection would take just a few minutes, and would involve a doctor making a small injection just below the surface of the eye in combination with numbing and cleaning the injection site. In the study, the researchers, including veterinary ophthalmologist and first author J. Jeremy Chae, did not observe significant inflammation resulting from the procedure.

The pressure reduction was sustained for four months. The researchers are now working to extend that time by modifying the polymer material — hyaluronic acid — with a goal of providing treatment benefits for at least six months. That would coincide with the office visit schedule of many patients.

“If we can get to a twice-a-year treatment, we would not disrupt the current clinical process,” Prausnitz said. “We believe the injection could be done as an office procedure during routine exams that the patients are already getting. Patients may not need to do anything to treat their glaucoma until their next office visit.”

Beyond extending the time between treatments, the researchers will need to demonstrate that the injection can be repeated without harming the eye. The procedure will also have to be tested in other animals before moving into human trials.

“The idea of having a ‘one-and-done’ treatment that lasts for six months would be particularly helpful for those whose access to healthcare is non-optimal,” Ethier said. “Having a long-acting therapy would have an additional advantage during times of pandemic or other disruption when access to healthcare is more difficult.”

This research was supported by a grant from the National Eye Institute (R01 EY025286) and by the Georgia Research Alliance. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies.

Mark Prausnitz serves as a consultant to companies, is a founding shareholder of companies, and is an inventor on patents licensed to companies developing microneedle-based products (Clearside Biomedical). These potential conflicts of interest have been disclosed and are being managed by Georgia Tech. J. Jeremy Chae, Jae Hwan Jung, Ethier, and Prausnitz are listed as co-inventors on an IP filing related to this study.

CITATION: J. Jeremy Chae, et al., “Drug-free, Non-surgical Reduction of Intraocular Pressure for Four Months After Suprachoroidal Injection of Hyaluronic Acid Hydrogel.” (Advanced Science, 2020) https://doi.org/10.1002/advs.202001908

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Biochemical information about the body most commonly comes from analysis of blood — which represents only 6% of bodily fluids — but valuable information may also be found in other bodily fluids that are traditionally hard to get. Researchers have now developed a way to extract dermal interstitial fluid (ISF), which circulates between cells in bodily tissues, using a simple through-the-skin technique that could provide a new approach for studying the metabolic products of cells, obtaining diagnostic biomarkers, and identifying potential toxins absorbed through the skin. Because the dermal interstitial fluid doesn’t clot like blood, the microneedle-based extraction could offer a new approach for continuous monitoring of glucose and other key health indicators.

Results of a human trial on the microneedle-based ISF sampling is reported Nov. 25 in the journal Science Translational Medicine. The study, conducted by researchers from the Georgia Institute of Technology and Emory University, was supported in part by the National Institutes of Health and Children’s Healthcare of Atlanta.

“Interstitial fluid originates in the blood and then leaks out of capillaries to bring nutrients to cells in the body’s tissues. Because interstitial fluid is in direct communication with the cells, it should have information about the tissues themselves beyond what can be measured from testing the blood,” said Mark Prausnitz, Regents Professor and J. Erskine Love Jr. Chair in Georgia Tech’s School of Chemical and Biomolecular Engineering. “This microneedle-based technique could provide a minimally invasive and simple way to access this interstitial fluid to make it available for medical diagnostic and research applications.” 

ISF has been difficult to sample. Indwelling instruments for monitoring glucose in ISF already exist, and other researchers have used surgically implanted tubing and vacuum-created blisters to extract ISF through the skin, but these techniques are not suitable for routine clinical diagnostic use. 

The researchers, led by first author Pradnya Samant, used a patch containing five solid stainless steel microneedles that were a hundredth of an inch in length. By pressing the patch at an angle into the skin of 50 human subjects, they created shallow micropores that reached only into the outer layer of skin containing ISF. The researchers then applied a suction to the area of skin containing the pores and obtained enough ISF to do three types of analysis. For comparison, they also took blood samples and obtained ISF using the older blister technique.

To accurately determine the biomarkers available in the ISF, the researchers needed to avoid getting blood mixed with the ISF. Though major blood vessels don’t exist in the outer layers of skin, capillaries there can be damaged by the insertion of the microneedles. In their studies, the researchers found that if they slowly ramped up the suction after inserting the microneedles, they could obtain fluid clear of blood.

The overall extraction procedure took about 20 minutes for each test subject. The procedure was well tolerated by the volunteers, and the microscopic pores healed quickly within a day, with minimal irritation.

The extracted fluid was analyzed at Emory University using liquid chromatography-mass spectrometry techniques to identify the chemical species it contained. Overall, there were about 10,000 unique compounds, most of which were also found in the blood samples. However, about 12% of the chemical species were not found in the blood, and others were found in the ISF at higher levels than in the blood.

“The skin is metabolically active, and it is full of cells that are changing the fluid,” Prausnitz said. “We found that some of the compounds were unique to the ISF, or enriched there, and that is what we were hoping to find.”

While not all the compounds unique to the ISF could be analyzed, the research team identified components of products that are applied to the skin — such as hand lotions — and pesticides that may enter the body through the skin. This discovery could set the stage for use of the microneedle technique for dermatological and toxicology studies.

“If you want to look at what accumulates in the skin over time, this may provide a way to obtain information about those kinds of exposures,” Prausnitz said. “These are materials that may accumulate in the tissues of our body, but are not found in the bloodstream.”

The researchers also determined the pharmacokinetics of caffeine and the pharmacodynamics of glucose — both small molecules — from the ISF, indicating that that dynamic biomarker information could be obtained from the technique. Those measurements suggested that ISF could provide a means for continuously monitoring such compounds, taking advantage of the fact that the fluid does not clot.

“We were encouraged that we found a good correlation between the blood and interstitial fluid glucose, which suggests we might be able to have a continuous glucose monitoring system based on this technology,” Prausnitz said. A microneedle-based system could provide a less invasive alternative to existing implantable glucose sensors by allowing the sensing components to remain on the surface of the skin.

In future research, Prausnitz would like to reduce the time required to extract the ISF and simplify the process by eliminating the vacuum pump. Additional study of the compounds found in the fluid could also show whether they have medical diagnostic value.

“We’d like to make this microneedle-based technique available to the research community to make ISF routinely available for study,” he said. “Tissue interstitial fluid could be a novel source of biomarkers that complements conventional sources. This research provides a means to study this further.”

The research team also included Nicholas Raviele and Juan Mena-Lapaix from Georgia Tech; and Megan M. Niedzwiecki, Douglas I. Walker, Gary W. Miller, Vilinh Tran, Eric I. Felner, and Dean P. Jones from Emory University.

CITATION: Pradnya P. Samant, "Sampling interstitial fluid for human skin using a microneedle patch." (Science Translational Medicine, 25 November 2020) https://stm.sciencemag.org/content/12/571/eaaw0285

This work was supported in part by the U.S. National Institutes of Health (U2CES026560, P30ES020953, R01ES023485, P30ES019776, S10OD018006) and by Children’s Healthcare of Atlanta. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies.

Mark Prausnitz is an inventor of patents licensed to companies developing microneedle-based products, is a paid advisor to companies developing microneedle-based products, and is a founder/shareholder of companies developing microneedle-based products (Micron Biomedical). This potential conflict of interest has been disclosed and is managed by Georgia Tech. Pradnya P. Samant and Prausnitz are inventors on a patent application (WO2019126735A1) submitted by Georgia Tech Research Corporation that covers ISF collection methods presented in this study.

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In a study published on March 9, 2020, in the journal Nature Medicine, Prausnitz and his team of researchers report on research using a skin cream infused with microscopic particles, named STAR particles. To the naked eye, STAR particles look like a powder, but closer inspection reveals tiny microneedle projections sticking out from the particles like a microscopic star. A particle-containing cream could potentially facilitate better treatment of skin diseases including psoriasis, warts, and certain types of skin cancer.

Following the successful study of his microneedle patches for vaccination, Prausnitz and postdoctoral scholar Andrew Tadros have advanced the technology with the objective of treating skin conditions by simply rubbing STAR particles on the skin. In a study in mice, skin cancer tumors were treated with 5-fluorouracil, a cancer therapy drug that works by limiting replication of abnormal cells. Tumor growth was inhibited only when the drug was rubbed on the skin above the tumor in combination with STAR particles, whereas the drug without STAR particles was much less effective.

“Andrew [Tadros] and I teamed up to adapt the microneedle technology and make it useful, especially in dermatology,” said Prausnitz, Regents Professor and J. Erskine Love Jr. Chair in the Georgia Tech School of Chemical and Biomolecular Engineering. “Microneedle patches are good at administering drugs or vaccines to a small area of skin, but many dermatological conditions are spread over larger areas. Rather than trying to make really big patches, which would be difficult to use, we ultimately arrived at STAR particles that can be rubbed on the skin – just like any skin lotion – and poke tiny holes in the skin to better deliver drugs.” 

STAR particles are mixed into a therapeutic cream or gel and applied to the skin, painlessly creating micropores in the skin’s surface that dramatically – but temporarily – increase skin permeability to drugs. 

The problem is that most drugs are not absorbed well into skin, so often a drug needs to be given to the whole body by pill or injection just to treat the skin. Exposing the whole body to dermatological drugs often leads to unwanted side effects such as nausea or organ damage. Fortunately, the barrier layer of skin – called the stratum corneum – is thinner than the width of a human hair. While STAR particles are tiny, they are large enough to poke through this barrier layer when rubbed on the skin and let drugs enter the body through the micropores without pain.

More effectively delivering medicine directly to where it’s needed could improve treatments for patients dealing with many kinds of skin diseases. Oral methotrexate is a common course of treatment for psoriasis –  a dermatological condition in which skin cells build up and form scales and itchy, dry patches – but because the therapy is systemic, it exposes the whole body to a drug that can cause serious side effects like diarrhea, hair loss, and liver problems. 

Prausnitz said doctors must weigh the costs of exposing the whole body to a drug versus treating psoriasis topically, which may be less effective. That’s where STAR particles could provide value. 

“Based on our studies, you could feasibly combine methotrexate with STAR particles into a cream and localize the therapy where it is needed,” Tadros said. “The STAR particles in the cream would enable drugs to get into skin and treat diseases locally, right where it needs to be treated, and without exposing the whole body to the drug.”

Skin creams that deliver drug therapies could widen the range of compounds administered topically, Prausnitz and Tadros suggested. Non-medicinal creams infused with STAR particles have been tested on humans, who generally reported experiencing a mild and comfortable tingling sensation, but no pain or skin irritation. 

Each STAR particle is no larger than a millimeter, with sharp and strong microneedle structures protruding from the surface that are 100 to 300 microns long. While the particles are barely perceptible to the human eye, the microneedles on them are not.

Moreover, when mixed in with a cream, the STAR particles disappear from sight. The research team uses a laser to make the particles from ceramic materials like titanium dioxide, a common ingredient in sunscreens and other cosmetic products. 

“Titanium dioxide is a common material that we have adapted to make STAR particles,” said Prausnitz. “The material is well established, but it’s the star-shaped geometry of the particle that’s new.” 

Prausnitz said he hopes to scale the STAR particles for commercial use not only in dermatology, but for cosmetic purposes as well, where they could potentially deliver anti-aging treatments without injections or other harsh procedures. 

“Our research philosophy is to develop an understanding of biomedical science and engineering technology, and then bring them together to create something that is practical and can benefit patients,” Prausnitz said. 

Prausnitz and Tadros have started a new company called Microstar Biotech that’s working to commercialize the STAR particle technology. 

“Georgia Tech has been instrumental in enabling us to bring this research to the forefront of the medical field, but universities can only do so much,” said Prausnitz. “Commercialization by a company is the mechanism to bring this novel research to the public for their benefit, and I’m hopeful for the future of STAR particles.” 

Results of the study are published in the March issue of the medical journal Nature Medicine. This work was supported financially by the Georgia Research Alliance and as a joint project of the CDC Foundation and UNICEF. 

Prausnitz and Tadros are inventors of the STAR particle technology used in this study and have ownership interest in Microstar Biotech LLC, which is developing technology related to this study. They are entitled to royalties derived from Microstar Biotech’s future sales of products related to the research. These potential conflicts of interest have been disclosed and are overseen by the Georgia Institute of Technology. 

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A report published recently in the Journal of Controlled Release describes a technique for administering contraceptive hormones through special backings on jewelry such as earrings, wristwatches, rings or necklaces. The contraceptive hormones are contained in patches applied to portions of the jewelry in contact with the skin, allowing the drugs to be absorbed into the body.

Initial testing suggests the contraceptive jewelry may deliver sufficient amounts of hormone to provide contraception, though no human testing has been done yet. A goal for the new technique is to improve user compliance with drug regimens that require regular dosages. Beyond contraceptives, the jewelry-based technique might also be used for delivering other drugs through the skin.

“The more contraceptive options that are available, the more likely it is that the needs of individual women can be met,” said Mark Prausnitz, a Regents Professor and the J. Erskine Love Jr. chair in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology. “Because putting on jewelry may already be part of a woman’s daily routine, this technique may facilitate compliance with the drug regimen. This technique could more effectively empower some women to prevent unintended pregnancies.”

This proof-of-concept research was supported by the U.S. Agency for International Development (USAID) under a subcontract funded by FHI 360.

Contraceptive jewelry adapts transdermal patch technology that is already used to administer drugs that prevent motion sickness, support smoking cessation, and control the symptoms of menopause, but have never been incorporated into jewelry before. Contraceptive patches are also already available, but Prausnitz believes pairing them with jewelry may prove attractive to some women – and allow more discreet use of the drug delivery technology.

“There is a lot of experience with making and using conventional transdermal patches,” he said. “We are taking this established technology, making the patch smaller and using jewelry to help apply it. We think that earring patches can expand the scope of transdermal patches to provide additional impact.” 

Postdoctoral Fellow Mohammad Mofidfar, Senior Research Scientist Laura O’Farrell and Prausnitz tested the concept on animal models, first on ears from pigs. Test patches mounted on earring backs and containing the hormone levonorgestrel were also applied to the skin of hairless rats. To simulate removal of the earrings during sleep, the researchers applied the patches for 16 hours, then removed them for eight hours. Testing suggested that even though levels dropped while the earrings were removed, the patch could produce necessary amounts of the hormone in the bloodstream.

The earring patch tested by the researchers consisted of three layers. One layer is impermeable and includes an adhesive to hold it onto an earring back, the underside of a wristwatch or the inside surface of a necklace or ring. A middle layer of the patch contains the contraceptive drug in solid form. The outer layer is a skin adhesive to help stick to skin so the hormone can be transferred. Once in the skin, the drug can move into the bloodstream and circulate through the body.

If the technique ultimately is used for contraception in humans, the earring back would need to be changed periodically, likely on a weekly basis.

The contraceptive jewelry was originally designed for use in developing countries where access to health care services may limit access to long-acting contraceptives such as injectables, implants and IUDs. However, Prausnitz says the technology may be attractive beyond that initial audience. “We think contraceptive jewelry could be appealing and helpful to women all around the world,” said Prausnitz.

The researchers tested patches adhered to earring backs, about one square centimeter in area, and placed them tightly on the skin of the test animals. Earring backs and watches may be most useful for administering drugs because they remain in close contact with the skin to allow drug transfer. The dose delivered by a patch is generally proportional to the area of skin contact.

“The advantage of incorporating contraceptive hormone into a universal earring back is that it can be paired with many different earrings,” Prausnitz noted. “A woman could acquire these drug-loaded earring backs and then use them with various earrings she might want to wear.”

Though transdermal drug-delivery patches have been available since 1979, testing would be required to determine whether the earring patch is safe and effective. In addition, research would be required to determine whether the concept would be attractive to women in different cultures.

“We need to understand not only the effectiveness and economics of contraceptive jewelry, but also the social and personal factors that come into play for women all around the world,” Prausnitz said. “We would have to make sure that this contraceptive jewelry concept is something that women would actually want and use.”

The technique could potentially be used to deliver other pharmaceuticals, though it would only be suitable for skin-permeable drugs that require administration of quantities small enough to fit into the patches. 

“We think there are uses beyond contraceptive hormones, but there will always be a limitation that the drug has to be effective with a low enough dose to fit into the limited space in the patch,” Prausnitz said. “It also should be a drug that would benefit from continuous delivery from a patch and that is administered to a patient population interested in using pharmaceutical jewelry.”

The earring patch is designed to add another contraceptive option for women. “Pharmaceutical jewelry introduces a novel delivery method that may make taking contraceptives more appealing,” he added. “Making it more appealing should make it easier to remember to use it.”

This work was made possible by the generous support of the American people through the U.S. Agency for International Development (USAID). The contents are the responsibility of the authors and do not necessarily reflect the views of FHI 360, USAID or the United States Government.  This research was supported by USAID cooperative agreement AID-OAA-15-00045 under a subcontract funded by FHI 360 as a proof-of-concept study (https://www.fhi360.org/projects/envision-fp).

CITATION: Mohammad Mofidfar, Laura O’Farrell and Mark R. Prausnitz, “Pharmaceutical jewelry: Earring patch for transdermal delivery of contraceptive hormone,” (Journal of Controlled Release, 2019) https://doi.org/10.1016/j.jconrel.2019.03.011

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The awards, which will be presented January 28 at Atlanta’s Fox Theatre, honor the department, institution, company or individuals who are forging new ground by thinking outside traditional paradigms to create unique technology.

Prausnitz, who holds the J. Erskine Love Jr. Chair at Georgia Tech's School of Chemical and Biomolecular Engineering, is being recognized for his success in translating science into useful products that will have a positive impact on the health of individuals and the population at large. He is the key scientific member of teams that have taken fundamental discoveries in microneedles and turned them into products to treat diseases of the eye and for cost-effective administration of vaccines to the global community.

Prausnitz leads a research group of more than 30 people working to develop novel mechanisms and technology to enhance and target drug and vaccine delivery for medical applications. His work has produced more than 220 research papers and more than 35 issued or pending U.S. patents (in addition to international filings).

In 2011, he co-founded Clearside Biomedical, which has raised $48 million in funding and is running three phase 2 or 3 clinical trials to treat inflammatory conditions in the back of the eye using the novel microneedle injection technology developed in Prausnitz’s lab.

In 2014, he co-founded Micron Biomedical, which is a clinical-stage company that seeks to commercialize microneedle patch technology developed in Prausnitz's lab for needle-free vaccination against influenza, polio and other diseases and self-administration of biopharmaceuticals without injections.

Georgia Bio is the state’s life science industry association whose members include pharmaceutical, biotechnology and medical device companies, medical centers, universities and research institutes, government groups and other business organizations involved in the development of life sciences related products and services.

Other winners of Georgia Bio's 2016 Innovation Award include NFANT Labs and Abeome Corporation.

Regents’ Professor Mark Prausnitz has been awarded the J. Erskine Love Jr. Chair in Chemical & Biomolecular Engineering (ChBE), a position previously held by Professor Chuck Eckert until his retirement in 2014.

Professors Chris Jones and Hang Lu have both been awarded Love Family Professorships.

“These positions are just part of an amazing legacy of generosity to Georgia Tech by the Love family, which now includes multiple endowed positions in ChBE and in other units on campus, as well as many other contributions,” says ChBE School Chair David Sholl.

“Mark, Hang, and Chris are all excellent examples of the ChBE aim to ‘Think Big, Solve Big.’ Their research is truly changing the world. It is wonderful to be able to honor their past and future accomplishments with these prestigious endowed positions.”

Long-time Tech supporter  J. Erskine Love Jr. (ME 1949) received the Georgia Tech Distinguished Service Award, the highest honor that can be bestowed upon alumni of the Institute.

The microneedle patch is designed to be administered by minimally trained workers and to simplify storage, distribution, and disposal compared with conventional vaccines.

The microneedle patch under development measures about a square centimeter and is administered with the press of a thumb. The underside of the patch is lined with 100 solid, conical microneedles made of polymer, sugar, and vaccine that are a fraction of a millimeter long. When the patch is applied, the microneedles press into the upper layers of the skin; they dissolve within a few minutes, releasing the vaccine. The patch can then be discarded.

“Each day, 400 children are killed by measles complications worldwide. With no needles, syringes, sterile water or sharps disposals needed, the microneedle patch offers great hope of a new tool to reach the world’s children faster, even in the most remote areas,” said James Goodson, Ph.D., epidemiologist from the CDC’s Global Immunization Division. “This advancement would be a major boost in our efforts to eliminate this disease, with more vaccines administered and more lives saved at less cost.”

Getting the measles vaccine to remote areas is expected to be easier because the patch is more stable at varying temperatures than the currently available vaccines and takes up less space than the standard vaccine. Because microneedles dissolve in the skin, there is no disposal of needles, reducing the risk of accidental needlesticks. The measles patch is expected be manufactured at a cost comparable to the currently available needle and syringe vaccine.

Twenty million people are affected by measles each year. Unfortunately, global coverage with the measles vaccine has been stagnant for the last few years at around 85 percent, which is well below the coverage of up to 95 percent needed to interrupt transmission of the disease.

Because measles is vaccine-preventable and the measles virus survives only in human hosts, the world’s health officials are aiming for measles elimination. Having a simple patch administered by minimally trained vaccinators could help increase vaccination coverage and achieve the goal of measles elimination.

Georgia Tech and CDC’s Global Immunization Division and Division of Viral Diseases recently completed a study that showed the new microneedle patch produces a strong immune response in an animal model. No adverse effects or health issues were noted during the study. These findings have cleared the way for developing proposals for human clinical trials, which could begin as early as 2017.

“We think this collaboration with CDC is an excellent example of how advances in engineering can be used to address important public health problems,” said Mark Prausnitz, a Regents Professor in the School of Chemical & Biomolecular Engineering at Georgia Tech. Prausnitz served as one of the principal investigators on the study.

World Immunization Week, celebrated in the last week of April each year, aims to promote the use of vaccines to protect people of all ages against disease. This year’s campaign focuses on closing the immunization gap and reaching equity in immunization levels as outlined in the Global Vaccine Action Plan (GVAP). The plan, endorsed by the 194 member states of the World Health Assembly in May 2012, is the framework to prevent millions of deaths by 2020 through universal access to vaccines for people in all communities.

The GVAP aims to:

• strengthen routine immunization to meet vaccination coverage targets; 
• accelerate control of vaccine-preventable diseases with polio eradication as the first milestone; 
• eliminate measles and rubella; 
• introduce new and improved vaccines; and 
• spur research and development for the next generation of vaccines and technologies.

Microneedle technology could move the GVAP forward by leading to improved protection against other diseases, including polio, influenza, rotavirus, rubella, tuberculosis and others. CDC is also collaborating with Georgia Tech to see if microneedles could be used to administer inactivated polio vaccine. Additional research is studying microneedle-administration of the influenza, rotavirus and tuberculosis vaccines.

To watch a video about microneedle technology please visit http://youtu.be/wVEF1ckaYEY.

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About the CDC
CDC works 24/7 saving lives and protecting people from health threats to have a more secure nation. Whether these threats are chronic or acute, manmade or natural, human error or deliberate attack, global or domestic, CDC is the U.S. health protection agency. CDC’s Global Immunization Division (GID) is involved in one of the most effective of all global public health missions – vaccination against deadly diseases – which saves the lives of 2 to 3 million people every year. GID works closely with a wide variety of partners to protect global citizens against contagious and life-threatening vaccine-preventable diseases.

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The designation honors those who “have demonstrated a highly prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on quality of life, economic development and the welfare of society.”

Prausnitz was chosen for the honor based on his revolutionary work in drug delivery technologies, especially microneedles, which are tiny needles (about 400 to 700 microns long) that can be designed as skin patches that provide a simple, painless and inexpensive way to administer influenza, polio, measles and other vaccines. Microneedles also can be prepared for microinjection into the eye for highly targeted therapies designed to increase drug effectiveness and safety.

“Our laboratory not only strives to advance scientific understanding and provide research training to students but also seeks to make inventions that can benefit society,” Prausnitz said.

Prausnitz will be honored at the NAI Fellows Luncheon and Induction Ceremony at the California Institute of Technology in Pasadena on March 20. The event is part of the organization’s annual conference.

Prausnitz also was named to the list of the World’s Most Influential Scientific Minds this year.

- Article courtsey of the Coulter Department of Biomedical Engineering at GT and Emory

The microneedles, ranging in length from 400 to 700 microns, could provide a new way to deliver drugs to specific areas within the eye relevant to these diseases. By targeting the drugs only to specific parts of the eye instead of the entire eye, researchers hope to increase effectiveness, limit side effects and reduce the amount of drug needed.

For glaucoma, which affects about 2.2 million people in the United States and is the second-leading cause of blindness worldwide, the goal is to develop time-release drugs that could replace daily administration of eye drops. A painless microneedle injection made once every three to six months – potentially during regular office visits – could improve treatment outcomes by providing consistent dosages and overcoming patient compliance issues.

In the second disease, corneal neovascularization, corneal injury results in the growth of unwanted blood vessels that impair vision. To treat it, the researchers developed solid microneedles for delivering a dry drug compound that stops the vessel growth.

“The power of microneedles for treating eye conditions is the ability to target delivery of the drug within the eye,” said Mark Prausnitz, a Regents’ professor in the School of Chemical & Biomolecular Engineering at the Georgia Institute of Technology. “We are developing different microneedle-based systems that can put the drug precisely into the part of the eye where it’s needed. In many cases, we hope to couple that delivery with a controlled-release formulation that would allow one application to treat a condition for weeks or months.”

To read more, follow this link.

The microneedles, ranging in length from 400 to 700 microns, could provide a new way to deliver drugs to specific areas within the eye relevant to these diseases. By targeting the drugs only to specific parts of the eye instead of the entire eye, researchers hope to increase effectiveness, limit side effects, and reduce the amount of drug needed.

For glaucoma, which affects about 2.2 million people in the United States and is the second leading cause of blindness worldwide, the goal is to develop time-release drugs that could replace daily administration of eye drops. A painless microneedle injection made once every three to six months – potentially during regular office visits – could improve treatment outcomes by providing consistent dosages, overcoming patient compliance issues.

In the second disease, corneal neovascularization, corneal injury results in the growth of unwanted blood vessels that impair vision. To treat it, the researchers developed solid microneedles for delivering a dry drug compound that stops the vessel growth.

“The power of microneedles for treating eye conditions is the ability to target delivery of the drug within the eye,” said Mark Prausnitz, a Regents’ professor in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology. “We are developing different microneedle-based systems that can put the drug precisely into the part of the eye where it’s needed. In many cases, we hope to couple that delivery with a controlled-release formulation that would allow one application to treat a condition for weeks or months.”

The research, which was supported by the National Eye Institute of the National Institutes of Health (NIH), was reported November 13 in the journal Investigative Ophthalmology & Visual Science. The research was done using animal models, and could become the first treatment technique to use microneedles for delivering drugs to treat diseases in the front of the eye.

Glaucoma results from elevated pressure inside the eye that can be treated by reducing production of the aqueous humor fluid in the eye, increasing flow of the fluid from the eye, or both. Glaucoma is now controlled by the use of eye drops, which must be applied daily. Studies show that as few as 56 percent of glaucoma patients follow the therapy protocol.

The microneedle therapy would inject drugs into space between two layers of the eye near the ciliary body, which produces the aqueous humor. The drug is retained near the injection side because it is formulated for increased viscosity. In studies with an animal model, the researchers were able to reduce intraocular pressure through the injections, showing that their drug got to the proper location in the eye.

Because the injection narrowly targets delivery of the drug, researchers were able to bring about a pressure reduction by using just one percent of the amount of drug required to produce a similar decline with eye drops. The research team, which also included Georgia Tech postdoctoral fellow Yoo Chun Kim and Emory University Emeritus Professor of Ophthalmology Henry Edelhauser, hopes to produce a time-release version of the drug that could be injected to provide therapy lasting for months.

“The ultimate goal for us would be for glaucoma patients visiting the doctor to get an injection that would last for the next six months, until the next time the patient needed to see the doctor,” said Prausnitz. “If we can do away with the need for patients to use eye drops, we could potentially have better control of intraocular pressure and better treatment of glaucoma.”

To treat corneal neovascularization, the researchers took a different approach, coating solid microneedles with an antibody-based drug that prevents the growth of blood vessels. They inserted the coated needles near the point of an injury, keeping them in place for approximately one minute until the drug dissolved into the cornea.

In an animal model, placement of the drug halted the growth of unwanted blood vessels for about two weeks after a single application. In addition to the researchers already mentioned, the corneal neovascularization research included Emory University Professor of Ophthalmology Hans Grossniklaus.

While the research reported in the journal did not include time-release versions of the drugs, a parallel project is evaluating potential formulations that would provide that feature.

Eye injections with hypodermic needles much larger than the microneedles are routinely used to administer compounds into the center of eye. These injections are well tolerated, and Prausnitz expects the use of microneedles would also not cause significant side effects.

“Increasingly, eye drops are not able to deliver drugs where they need to go, so injections into the eye are becoming more common,” said Edelhauser. “But hypodermic needles were not designed for the eye and are not optimal for targeting drugs within the eye.”

In contrast to the larger hypodermic needles, the microneedles are tailored to penetrate the eye only as far as needed to deliver the drugs to internal spaces within the layers of the eye. For the glaucoma drug, for instance, the needle is only about half a millimeter long, which is long enough to penetrate through the sclera, the outer layer of the eye, to the supraciliary space.

Both potential treatments would require additional animal testing before human trials could begin.

Yoo C. Kim, Henry F. Edelhauser, and Mark R. Prausnitz hold microneedle patents, and Mark Prausnitz and Henry Edelhauser have significant financial interest in Clearside Biomedical, a company developing microneedle-based products for ocular delivery. This potential conflict of interest has been disclosed and is overseen by Georgia Institute of Technology and Emory University.

CITATIONS: Yoo C. Kim, Henry F. Edelhauser and Mark R. Prausnitz, “Targeted Delivery of Antiglaucoma Drugs to the Supraciliary Space Using Microneedles,” (Investigative Ophthalmology & Visual Science, 2014) and Yoo C. Kim, Hans E. Grossniklaus, Henry F. Edelhauser and Mark R. Prausnitz, “Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization,” (Investigative Ophthalmology & Visual Science, 2014).

Research reported in this news release was supported by the National Eye Institute of the National Institutes of Health under award numbers R01EY022097 and R24EY017045. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Writer: John Toon

The research, which involved nearly 100 people recruited in the metropolitan Atlanta area, found that test subjects could successfully apply a prototype vaccine patch to themselves. That suggests the self-administration of vaccines with microneedle patches may one day be feasible, potentially reducing administration costs and relieving an annual burden on health care professionals.

The study also suggested that the use of vaccine patches might increase the rate at which the population is vaccinated against influenza. After comparing simulated vaccine administration using a patch and by conventional injection, the percentage of test subjects who said they’d be vaccinated grew from 46 percent to 65 percent.

“Our dream is that each year there would be flu vaccine patches available in stores or sent by mail for people to self-administer,” said Mark Prausnitz, a Regent’s professor in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology. “People could take them home and apply them to the whole family. We want to get more people vaccinated, and we want to relieve health care professionals from the burden of giving these millions of vaccinations.”

The research on patient acceptance of vaccine patch immunization was published online February 11, 2014, by the journal Vaccine and will appear in a later edition of the print journal. In addition to Georgia Tech researchers, the project also included scientists from Emory University and the Centers for Disease Control and Prevention (CDC). Research into the use of microneedle patches for influenza vaccination has been supported by the National Institutes of Health (NIH).

The study is believed to be the first published report of a head-to-head comparison between microneedle patches and traditional intramuscular injection for the administration of vaccines in human subjects. The patches consisted of arrays of 50 microscopic needles about as tall as the thickness of a few hairs. When used for vaccination, the patches would be pressed painlessly onto a person’s forearm to carry vaccine into the outer layers of skin, where they would prompt an immune reaction from the body.

The 91 study subjects, who had no previous experience with microneedle patches, were given brief instructions on applying the patches to themselves. Each volunteer applied three patches, had a fourth patch applied by a member of the research team, and received an injection of saline with a conventional hypodermic needle. Neither the patches nor the hypodermic needle actually carried a vaccine, and the study did not assess the efficacy of using microneedle patches for vaccinations in humans.

The researchers evaluated how well the volunteers were able to self-administer the microneedle patches. After the subjects pressed the patches into their skin, the researchers applied a dye to highlight the tiny holes made by the microneedles. By photographing the administration sites and counting the number of holes, they were able to assess the accuracy of the application.

“We found that everyone was capable of administering a microneedle patch appropriately, though not everyone did on the first try,” Prausnitz said.

Some of the subjects used an applicator that made a clicking sound when sufficient force was applied to the patch. Use of that feedback device improved the ability of subjects to correctly apply patches and virtually eliminated administration mistakes.

During the study, the volunteers were asked if they planned to receive a flu vaccination in the next year and if their intent to be vaccinated would change if it could be done with the patch. The percentage saying they’d be vaccinated jumped from 46 to 65 percent when the patch was an option.

“If this holds for the population as a whole, that would have a tremendous impact on preventing disease and the cost associated with both influenza and the vaccination process,” said Paula Frew, an assistant professor in the Emory University School of Medicine and a co-author of the study.

Interviewing the test subjects found strong support for self-administration of the flu vaccine.

“In addition to the preference for the vaccine patch, we found that a large majority of the people willing to be vaccinated would choose to self-administer the vaccine,” said James Norman, the study’s first author, who was a Georgia Tech graduate student when the research was conducted.  

Study participants were asked to assess the pain associated with administering the patch and receiving the intramuscular injection. On a scale of one to 100, they rated the patches 1.5 on average, while the injection was rated 15.

Less than half the U.S. population receives vaccination against influenza each year. Several thousand Americans die of complications from the flu each year, and as many as 200,000 are hospitalized. Increasing the immunization rate could cut the deaths, hospitalizations and costs associated with the disease, Prausnitz noted.

Use of a vaccine patch could potentially also reduce the cost of vaccination programs. For influenza, the cost of storing and administering the vaccine – along with patient time to visit a clinic – accounts for as much as three-quarters of the total cost. If microneedle vaccine patches could be produced for about the same cost as current flu vaccines, self-administration could provide significant cost savings to the nation’s health care system.

Animal studies have shown that microneedle patches are at least as good as conventional intramuscular injections at conferring immunity to influenza. Prausnitz and his research team plan to begin a Phase 1 clinical study of the vaccine patches in humans during the spring of 2015. If that study shows promise, it could lead to larger studies and development of commercial patch manufacture.

If all goes well, the vaccine patch could be available within five years. Prausnitz expects it to be administered first by health care professionals before being made available for self-administration.

In addition to those already named, the study also involved Martin I. Meltzer, senior health economist with the CDC, and two Georgia Tech researchers: Jaya M. Arya and Maxine A. McClain.

Mark Prausnitz is an inventor on patents that have been licensed to companies developing microneedle-based products, is a paid advisor to companies developing microneedle-based products, and is a founder/shareholder of companies developing microneedle-based products. This potential conflict of interest has been disclosed and is managed by Georgia Tech and Emory University.

Research on the use of microneedle patches for influenza vaccination has been supported by the National Institute of Biomedical Imaging and Bioengineering, part of the National Institutes of Health (NIH/NIBIB), under award R01EB006369. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

CITATION: James J. Norman, et al., “Microneedle Patches: Usability and Acceptability for Self-Vaccination Against Influenza,” (Vaccine, 2014). (http://dx.doi.org/10.1016/j.vaccine.2014.01.076)

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Media Relations Contacts: John Toon (404-894-6986) (jtoon@gatech.edu) or Brett Israel (404-385-1933) (brett.israel@comm.gatech.edu).

Writer: John Toon

The new funding is in addition to a $4 million venture capital investment received by Clearside Biomedical in early 2012 that served as the foundation for the startup company.

Santen Pharmaceuticals Co., Ltd in Osaka, Japan, will fund Clearside’s technology development, and has also entered into a research collaboration agreement for posterior ocular diseases. Santen, along with new investor Mountain Group Capital and its affiliates, joins current investors Hatteras Venture Partners in Durham, NC, the Georgia Research Alliance Venture Fund, and the University of North Carolina’s Kenan Flagler Business School Private Equity Fund.

Clearside Biomedical is developing microinjection technology that uses hollow microneedles to precisely deliver drugs to a targeted area at the back of the eye. If the technique proves successful in clinical trials and wins regulatory approval, it could provide an improved method for treating diseases including age-related macular degeneration and glaucoma, as well as other ocular conditions related to diabetes.

The technology was developed in a collaboration between the research groups of Henry Edelhauser, PhD, professor of ophthalmology at Emory University School of Medicine, and Mark Prausnitz, PhD, a Regents’ professor in Georgia Tech’s School of Chemical and Biomolecular Engineering. The National Institutes of Health sponsored research leading to development of the technology.

In contrast to standard treatments, this microneedle technology provides a more targeted approach for treating retinal diseases that confines the drug to the site of disease and reduces side effects from exposing other parts of the eye. Prior to the development of this technology, drugs could be delivered to the retinal tissues at the back of the eye in three ways: injection by hypodermic needle into the eye’s vitreous humor (the gelatinous material that fills the eyeball); eye drops, which have limited ability to reach the back of the eye; and pills taken by mouth that expose the whole body to the drug.

The technology developed by Georgia Tech and Emory uses a hollow micron-scale needle to inject drugs into the suprachoroidal space located between the outer surface of the eye – known as the sclera – and the choroid, a deeper layer that provides nutrients to the rest of the eye. Preclinical research has shown that fluid can flow between the two layers, where it can spread out along the circumference of the eye, targeting structures like the choroid and retina that are now difficult to reach.

By targeting the suprachoroidal space using microscopic needles, the researchers believe they can reduce trauma to the eye, make drugs more effective and reduce complications. The new delivery method could help advance a new series of drugs being developed to target the retina, choroid and other structures in the back of the eye.

“I cannot imagine a better alliance as we continue to understand the role the suprachoroidal space will play in dosing medicine directly to the site of retinal disease in patients experiencing retinal blindness,” says Daniel White, president and CEO of Clearside Biomedical. “The collaboration with Santen prepares an avenue to develop state-of-the-art medications for the critical treatment of sight-threatening diseases.”

In November 2012, Clearside announced its first successful human dosing with the device in a safety and tolerability study in patients with retinal disease.

The U.S. Food and Drug Administration has allowed Clearside Biomedical to pursue testing related to its Investigational New Drug (IND) Application for CLS1001 (triamcinolone acetonide) Suprachoroidal Injectable Suspension. This IND would treat sympathetic ophthalmia, temporal arteritis, uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids. Clinical testing is scheduled to proceed within the next few months.

Samirkumar Patel and Vladimir Zarnitsyn, researchers from the Prausnitz lab who were involved in development of the ocular drug delivery technique, have joined Clearside Biomedical. Edelhauser serves as vice president of scientific affairs and Prausnitz serves on the board of directors of Clearside Biomedical.

The company was formed with the assistance of Georgia Tech’s VentureLab program, Georgia Tech’s center for commercialization, serving faculty, staff and students who want to form startup companies based upon their research or invention.

Henry Edelhauser, Samirkumar Patel, Mark Prausnitz, Vladimir Zarnitsyn, Emory University and Georgia Tech have financial interests in Clearside Biomedical and its ocular platform and own equity in Clearside. The terms of this arrangement have been reviewed and approved by Emory University and Georgia Tech in accordance with their conflict of interest policies.

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Media Relations Contacts: Georgia Tech, John Toon (jtoon@gatech.edu)(404-894-6986) or Emory University, Holly Korschun (hkorsch@emory.edu)(404-727-3990).

Writer: Holly Korschun

“This year’s GAANN fellows were selected from an outstanding pool of applicants, who are carrying out high-impact research addressing a broad range of pharmaceutical needs” said Mark Prausnitz, PhD, Regents' professor and Love Family professor in Chemical & Biomolecular Engineering and director of CD4, who serves as the principle investigator of the program. 

The new class of fellows represent a diverse group of students from biomedical engineering, chemistry, chemical and biomolecular engineering and materials science and engineering.  

“While most academic training programs address one particular aspect of pharmaceutical research, at Georgia Tech, we have an integrative approach that brings together scientists and engineers from many disciplines to improve the process of pharmaceutical development that includes drug design, manufacturing and delivery. Through the GAANN training grant, we are training future leaders of pharmaceutical research who understand the complex, interconnected process of bringing a drug from idea to product,” Prausnitz added

Since the program’s inception in 2003, over 130 fellowships have been awarded.  Solicitation for the 2013-2013 fellows will take place beginning in April 2013.

The 2012-2013 GAANN fellows:

Rayaj Ahmed – Chemistry & Biochemistry
Samantha Au – Chemical & Biomolecular Engineering
W. Chris Edens – Biomedical Engineering
Hiroyuki Ichikawa – Chemistry & Biochemistry
Russell Jampol – Chemical & Biomolecular Engineering
Yoo Chun Kim – Chemical & Biomolecular Engineering
Jonathan Park – Chemical & Biomolecular Engineering
Michelle Razumov – Chemistry & Biochemistry
Mark Spears – Chemistry & Biochemistry
Maeling Tapp – Material Science and Engineering
Aubrey Tiernan – Chemical & Biomolecular Engineering
Alex Weller – Material Science and Engineering
Jenna Wilson – Biomedical Engineering 

For the first time, researchers from the Georgia Institute of Technology and Emory University have demonstrated that microneedles less than a millimeter in length can deliver drug molecules and particles to the eye in an animal model. The injection targeted the suprachoroidal space of the eye, which provides a natural passageway for drug injected across the white part (sclera) of the eye to flow along the eye’s inner surface and subsequently into the back of the eye. The minimally-invasive technique could represent a significant improvement over conventional methods that inject drugs into the center of the eye – or use eyedrops, which have limited effectiveness in treating many diseases.

The study was reported in the July issue of the journal Investigative Ophthalmology & Visual Science. The research was supported by the National Eye Institute, which is part of the National Institutes of Health, and by the organization Research to Prevent Blindness.

“This research could lead to a simple and safe procedure that offers doctors a better way to target drugs to specific locations in the eye,” said Samirkumar Patel, the paper’s first author and a postdoctoral researcher at Georgia Tech when the research was conducted. “The design and simplicity of the microneedle device may make it more likely to be used in the clinic as a way to administer drug formulations into the suprachoroidal space that surrounds the eye.”

Patel, who is now director of research for Clearside Biomedical – a startup company formed to commercialize the technology – said the study also showed that the suprachoroidal space could accommodate a variety of drugs and microparticles. That could open the door for the use of timed-release drugs that could reduce the need for frequent injections to treat chronic eye diseases.

The suprachoroidal space is located between two important structures in the eye: the sclera and the choroid. Fluids injected into that space travel circumferentially around the eye, which flows drug solution directly over the choroid and adjacent retina – which are the targets for many drug compounds. The new study showed that injections of fluids containing molecules and particles into that space not only reach the targeted structures, but also remain there for extended time periods. And equally important, the molecules and particles do not significantly reach the lens or front part of the eye, where side effects from drugs can occur.

“The study showed that if we inject non-degradable particles into the suprachoroidal space and wait as long as two months, the particles remain,” said Mark Prausnitz, a Regents professor in Georgia Tech’s School of Chemical and Biomolecular Engineering. “That means there is no natural mechanism to remove the particles from the eye. Knowing this, we can design biodegradable particles with drugs encapsulated in them that can slowly release those drugs over a period of time that we could control.”

Currently, doctors typically have two choices for administering drugs to the eye: eye drops and injection with a traditional hypodermic needle into the vitreous at the center of the eye. While injections into the vitreous do reach their target, they also affect other portions of the eye where the drug may not be desirable. Eye drops, which are simple to use, often fail to reach the structures being targeted, Prausnitz said.

Henry Edelhauser, a professor of ophthalmology at Emory School of Medicine, said pharmaceutical companies are now developing new compounds to treat eye diseases. Those drugs will be most effective if they can be delivered directly to the portion of the eye that requires treatment, such as the choroid and retina that this new delivery method targets.

“With this technique, we are keeping the drug right where it needs to be for most therapies of interest in the back of the eye,” he said.

The microneedles used in the technique are made of stainless steel and are less than one millimeter long. The researchers believe that they will cause less trauma to the eye than the larger hypodermic needles, and reduce the risk of infection.

The model compounds used in this study fluoresced inside the eye, showing researchers that they had reached their targets. But the compounds studied were not drugs, so the next step, according to Edelhauser, will be to study how well the microneedle technique can get real drugs to the eye structures of interest.

The technology has been licensed to an Atlanta-based startup, Clearside Biomedical, which plans to advance the micro-injection technology developed in collaboration between the research groups of Mark Prausnitz at Georgia Tech and Henry Edelhauser at Emory.

Clearside Biomedical was formed with the assistance of Georgia Tech’s VentureLab program, which helped obtain early-stage seed funding from the Georgia Research Alliance. Clearside has received $4 million in funding mostly from Hatteras Venture Partners, a venture capital firm based in Durham, N.C.

In addition to those already mentioned, the study involved Damian Berezovsky and Bernard McCarey from the Emory Eye Center in the Emory University School of Medicine, and Vladimir Zarnitsyn from the Georgia Tech School of Chemical and Biomolecular Engineering.

Development of the intraocular microneedle demonstrates the strength of collaboration between researchers at Emory University and Georgia Tech.

“This project leveraged the skills of both institutions and came up with a solution that we could never have developed independently,” Prausnitz said. “With support from the National Institutes of Health, we have developed a solution that could give patients with eye diseases the medication they need in a more effective way.”

Henry Edelhauser, Samirkumar Patel, Mark Prausnitz, Vladimir Zarnitsyn, Emory University and Georgia Tech have financial interests in Clearside Biomedical and its ocular platform. Edelhauser, Patel, Prausnitz and Zarnitsyn own equity in Clearside and the terms of this arrangement have been reviewed and approved by Emory University or Georgia Tech in accordance with their conflict of interest policies.

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Two dozen students from Georgia Tech, Mercer University, Georgia State University and Emory University heard lectures from Atlanta-based medical professionals, researchers, and pharmaceutical company leaders – and worked in teams to develop plans for how a drug company might convert a promising molecule into a real product. To demonstrate the interdisciplinary nature of the drug development process, each team included pharmacists, bio-scientists, chemists and engineers.

“Each team was given information from the scientific literature on a drug in early stage development by a pharmaceutical company, and was asked to put together and justify a detailed plan for bringing that molecule forward into a drug product useful in clinical medicine,” said Mark Prausnitz, the course’s leader and a Regents’ professor in Georgia Tech’s School of Chemical & Biomolecular Engineering.

Speakers from the Atlanta pharmaceutical community talked to the students on such topics as drug discovery and design, drug manufacturing, formulation, pre-clinical studies, design of clinical trials, marketing, project teamwork and R&D reports. In addition to Prausnitz, other instructors included:

• Ajay Banga, professor and chair of pharmaceutical sciences at Mercer University;
• Andy Bommarius, professor of chemical & biomolecular engineering at Georgia Tech;
• Bobby Khan, chief medical officer at Atlanta Clinical Research Centers;
• Joseph Patti, co-founder and senior vice president of R&D at Inhibitex;
• Harold Shlevin, director of bioscience commercialization at Georgia Tech and former CEO of Solvay Pharmaceuticals;
• James Sikorski, a consultant and former vice president of medicinal chemistry at AtheroGenics;
• Jaipal Singh, adjunct professor of biology at Georgia Tech and former chief scientific officer at Saint Joseph’s Translational Research Institute;
• Charlie Thompson, a principal at Axtria;
• Wes Wynans, director of leadership education and development at Georgia Tech.

Students were pleased with the opportunity to see the entire drug development process and to work closely with peers from other universities. “Working in an interdisciplinary team allowed us to connect the dots between all of the medical, scientific and business aspects of bringing a drug to the market,” said Meera Gujjar, a graduate student in pharmaceutical sciences at Mercer University. 

Chris Quinto, a Ph.D. student from Georgia Tech, found students from other backgrounds helpful in sharing their expertise in the complex drug development process.

“The Mercer students in my group were a great resource in helping explain and make sense of the data and terminology in the papers that we read,” Quinto said. “What I found most interesting in this class was how the drug development research teams consist of many different specialties, each of which is vital to the final outcome of the drug development process.”

The course is expected to be offered once every two years. “This shows how Atlanta universities are working together and with local pharmaceutical companies to build a stronger pharmaceutical research and education community here,” Prausnitz added.

The Atlanta-based startup, Clearside Biomedical, plans to develop microinjection technology that will use hollow microneedles to precisely target therapeutics within the eye. If the technique proves successful in clinical trials and wins regulatory approval, it could provide an improved method for treating diseases that affect the back of the eye, including age-related macular degeneration.

The technology was developed in collaboration between the research groups of Mark Prausnitz, a Regents' professor in Georgia Tech's School of Chemical and Biomolecular Engineering, and Henry Edelhauser, a professor in the Department of Ophthalmology at Emory School of Medicine. Research leading to development of the technology was sponsored by the National Institutes of Health (NIH).

"We expect that targeting drug delivery within the eye will be helpful because we should be able to concentrate drugs at the disease sites where they need to act, and keep them away from other locations," said Prausnitz. "This could reduce side effects and possibly also decrease the dose required."

Prior to this development, drugs could be delivered to the retinal tissues at the back of the eye in three indirect ways: (1) injection by hypodermic needle into the eye's vitreous humor, the gelatinous material that fills the eyeball, (2) eye drops, which are limited in their ability to reach the back of the eye, and (3) pills taken by mouth that expose the whole body to the drug.

The technology developed by Georgia Tech and Emory uses a hollow micron-scale needle to inject therapeutics into the suprachoroidal space located between the outer surface of the eye -- known as the sclera -- and the choroid -- a deeper layer that provides nutrients to the rest of the eye. Preclinical research has demonstrated that fluid can flow between the two layers, where it can spread out to the entire eye, including structures such as the retina that are now difficult to reach.

By targeting this suprachoroidal space using microscopic needles, the researchers believe they can reduce trauma to the eye, make drugs more effective and reduce complications. The new delivery method could help advance a new series of drugs being developed to target the retina, choroid and other structures in the back of the eye.

"This is a significant advance in the field of ophthalmology," said Edelhauser. "Until now, it has been difficult to target drug delivery to specific locations within the eye. This new microneedle technology enables precise drug targeting to the suprachoroidal space and other locations within the eye."

In research reported in the January 2011 issue of the journal Pharmaceutical Research, the Georgia Tech-Emory team demonstrated for the first time that this technique can be used to deliver nanoparticles and microparticles to specific parts of the eye. In later research, they also showed that microneedle injections into the suprachoroidal space rapidly resulted in concentrations of drugs and particles that could be maintained for several months.

Between two and three million eye injections are made each year, many of them to treat age-related macular degeneration (AMD). The researchers believe that the microneedle-based technique could be useful for treating both AMD and glaucoma, as well as other ocular conditions related to diabetes.

The $4 million in funding for Clearside Biomedical will come from Hatteras Venture Partners, a venture capital firm based in Research Triangle Park, N.C. Hatteras focuses on seed and early-stage investments in companies developing products in biopharmaceutical, medical device, diagnostic and related human health areas.

"Clearside Biomedical represents an ideal fit for Hatteras Discovery as the platform technology is highly innovative, based on elegant science and the lead product is expected to be in clinical trials in the United States in less than 18 months," said Christy Shaffer, Ph.D., venture partner and managing director of the Hatteras Discovery Fund.

So far, the technique has been tested only in animals. The Hatteras funding will allow the company to conduct additional efficacy and safety testing needed to seek regulatory approval. The company's first product is expected to address macular edema and retinal vein occlusion.

Clearside was formed with the assistance of Georgia Tech's VentureLab program, which helped obtain early-stage seed funding from the Georgia Research Alliance. Georgia Tech VentureLab also helped the founders connect with the company's president and CEO, Daniel White, a veteran ophthalmic entrepreneur. Before joining Clearside, White was a co-founder of Alimera Sciences, an Atlanta company that is developing ophthalmic pharmaceuticals.

Two researchers from the Prausnitz lab who have been involved in development of the ocular drug delivery technique will also join the company. They are Samirkumar Patel, a postdoctoral researcher and Vladimir Zarnitsyn, a research scientist.

Research leading to the development of the technology has been supported by the National Institutes of Health (NIH). The content of this article is solely the responsibility of the principal investigators and does not necessarily represent the official view of the NIH.

Henry Edelhauser, Samirkumar Patel, Mark Prausnitz, Vladimir Zarnitsyn, Emory University and Georgia Tech have financial interests in Clearside Biomedical and its ocular platform. Edelhauser, Patel, Prausnitz and Zarnitsyn own equity in Clearside and the terms of this arrangement have been reviewed and approved by Emory University or Georgia Tech in accordance with their conflict of interest policies.

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Media Relations Contacts: Georgia Tech -- John Toon (404-894-6986)(jtoon@gatech.edu) or Abby Robinson (404-385-3364)(abby@innovate.gatech.edu); Emory University -- Holly Korschun (404-727-3990)(hkorsch@emory.edu).

Writer: John Toon

Grand Challenges Explorations funds scientists and researchers worldwide to explore ideas that can break the mold in how we solve persistent global health and development challenges. The Georgia Tech/CDC project is one of 110 Grand Challenges Explorations grants announced November 7th.

"We believe in the power of innovation -- that a single bold idea can pioneer solutions to our greatest health and development challenges," said Chris Wilson, director of global health discovery for the Bill & Melinda Gates Foundation. "Grand Challenges Explorations seeks to identify and fund these new ideas wherever they come from, allowing scientists, innovators and entrepreneurs to pursue the kinds of creative ideas and novel approaches that could help to accelerate the end of polio, cure HIV infection or improve sanitation."

Projects that are receiving funding show promise in tackling priority global health issues where solutions do not yet exist. This includes finding effective methods to eliminate or control infectious diseases such as polio and HIV as well as discovering new sanitation technologies.

The goal of the Georgia Tech/CDC project is to demonstrate the scientific and economic feasibility for using microneedle patches in vaccination programs aimed at eradicating the polio virus. Current vaccination programs use an oral polio vaccine that contains a modified live virus. This vaccine is inexpensive and can be administered in door-to-door immunization campaigns, but in rare cases the vaccine can cause polio. There is an alternative injected vaccine that uses killed virus, which carries no risk of polio transmission, but is considerably more expensive than the oral vaccine, requires refrigeration for storage and must be administered by trained personnel. To eradicate polio from the world, health officials will have to discontinue use of the oral vaccine with its live virus, replacing it with the more expensive and logistically-complicated injected vaccine.

Prausnitz and his CDC collaborators believe the use of microneedle patches could reduce the cost and simplify administration of the injected vaccine. Use of the patches, which carry vaccine into the body by dissolving into the skin, could eliminate the need for administration by highly-trained personnel and the "sharps" disposal problems of traditional hypodermic needles. Because skin administration produces an immune response with smaller doses of vaccine than traditional deep intramuscular injection, the researchers expect to reduce the per-person cost of vaccine. And by incorporating dried vaccine into the microneedles, they hope to eliminate the need for vaccine refrigeration -- a challenge in remote areas of the world.

"We envision vaccination campaigns in which minimally-trained personnel go door-to-door administering microneedle patches rather than oral polio vaccine," Prausnitz explained. "Our goal for this study will be to provide the data to scientifically justify moving the microneedle patch for polio vaccination into a human trial."

In research that will complement the Grand Challenges Exploration grant, Prausnitz and his team have also received funding from the World Health Organization (WHO) to support development of the polio vaccine application for microneedle patches. And in a project sponsored by the U.S. National Institutes of Health (NIH), Prausnitz and other Georgia Tech researchers are collaborating with Emory University scientists on development of a microneedle patch for administering flu vaccine.

About Grand Challenges Explorations: Grand Challenges Explorations is a US $100 million initiative funded by the Bill & Melinda Gates Foundation. Launched in 2008, Grand Challenge Explorations grants have already been awarded to nearly 500 researchers from over 40 countries. The grant program is open to anyone from any discipline and from any organization. The initiative uses an agile, accelerated grant-making process with short, two-page online applications and no preliminary data required. Initial grants of $100,000 are awarded two times a year. Successful projects have an opportunity to receive a follow-on grant of up to US $1 million. To learn more about Grand Challenges Explorations, visit www.grandchallenges.org.

About The Georgia Institute of Technology: The Georgia Institute of Technology is one of the world's premier research universities, ranked second among all U.S. colleges and universities in the amount of engineering research conducted. Ranked seventh among U.S. News & World Report's top public universities, Georgia Tech's more than 20,000 students are enrolled in its Colleges of Architecture, Computing, Engineering, Liberal Arts, Management and Sciences. Georgia Tech is among the nation's top producers of women and minority engineers. The Institute offers research opportunities to both undergraduate and graduate students and is home to more than 100 interdisciplinary units plus the Georgia Tech Research Institute.

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Media Relations Contacts: John Toon (404-894-6986)(jtoon@gatech.edu) or Abby Robinson (404-385-3364)(abby@innovate.gatech.edu).

Mice given a single H1N1 vaccine through the skin using a coated metal microneedle patch as well as mice vaccinated through subcutaneous injection were 100 percent protected against a lethal flu virus challenge six weeks after vaccination. However, when challenged with the H1N1 virus six months later, the injected mice had a 60 percent decrease in antibody production against the virus and extensive lung inflammation. Mice that were vaccinated with microneedles, on the other hand, maintained high levels of protection and antibody production after six months, with no signs of lung inflammation.

"A major goal of influenza vaccine development has been to confer strong immune responses, including immunological memory and cellular immune responses for long-term protection, and to limit virus spread after infection," said first author Dimitrios Koutsonanos, MD, post-doctoral fellow of microbiology and immunology at Emory University School of Medicine.

The research team also included Ioanna Skountzou, MD, PhD, Richard Compans, PhD, Maria del Pilar Martin, PhD, and Joshy Jacob, PhD, from Emory, and Georgia Tech bioengineers Mark Prausnitz, PhD, and Vladimir Zarnitsyn, PhD.

Researchers already have found that intramuscular injection is not the most efficient way to deliver vaccines. The muscles have a low concentration of cells needed to relay immune signals and activate a T-cell response, including dendritic cells, macrophages, and MHC class II-expressing cells. The skin, however, contains a rich network of antigen-presenting cells, including macrophages, Langerhans cells and dermal dendritic cells that activate cytokines and chemokines – immune signaling cells responsible for initiating an immune response.

The Emory/Georgia Tech research team previously reported that delivery of seasonal influenza vaccine through the skin using antigen-coated metal microneedle patches or dissolving microneedles elicited strong immune responses that can confer protection at least equal to conventional intramuscular injections. The team has developed dissolving microneedle technology that could be used in easy-to-administer, painless patches.

"The pandemic H1N1 A/California/04/09 influenza virus continues to be the predominant strain," said lead researcher Ioanna Skountzou, MD, PhD, assistant professor of microbiology and immunology at Emory University School of Medicine. "Our research shows that skin-based vaccination, made possible through microneedle technology, may now be a viable and more effective alternative to intramuscular injection for H1N1 flu and other strains as well."

"Microneedle delivery also offers other logistical advantages that make this method attractive for influenza vaccination, such as inexpensive manufacturing, small size for easy storage and distribution, and simple administration that might enable self-vaccination to increase patient coverage," said Prausnitz.

This news release was written by Emory University.

Media Contacts: Holly Korschun, Emory University (404-727-3990)(hkorsch@emory.edu) or John Toon (404-894-6986)(jtoon@gatech.edu).

The project focuses on the development of an effective vaccine for Ebola and Marburg virus infections, two members of a family named "filoviruses" because they produce long filamentous particles.

The lead investigators include Richard Compans and Chinglai Yang at Emory University, Mark Prausnitz at Georgia Tech, and Jean Patterson and Ricardo Carrion at Texas Biomedical Research Institute.

According to Compans, "These viruses cause severe hemorrhagic fevers with up to 90 percent mortality, and can be passed via person-to-person contact, thus posing a high risk in case of an epidemic outbreak as well as a possible bioterrorism threat.”

In ongoing research, the Emory group has developed virus-like particle (VLP) vaccines to prevent virus infection, and has shown that the Ebola VLPs stimulate immune cell activity and induce strong antibody responses, indicating that such VLPs could be effective vaccines to induce protective immunity against infection. They also have found that immunization with a mixture of DNA and VLP vaccines (DNA/VLP) induced higher levels of protective immune responses in comparison to immunization with either vaccine alone.

"We consider this to be one of the most promising and safest approaches to protecting against hemorrhagic fever viruses," said Patterson, chair of the Department of Virology and Immunology at Texas Biomedical Research Institute.

In addition, the researchers are testing these vaccines with a new skin delivery technology developed at Georgia Tech that could further increase such responses, with the aim of having a vaccine that can confer rapid and long-lasting protection against Ebola and Marburg virus infection. The results will identify the most effective candidate vaccine for human trials. The successful development of this vaccine strategy may also lead to vaccines against other viral hemorrhagic fevers, which still lack effective vaccines.

"Administering these vaccines with a microneedle skin patch may increase the effectiveness of the vaccine, as well as potentially make vaccination simple and painless," said Prausnitz, professor of chemical and biomedical engineering at Georgia Tech.

The Robert W. Woodruff Health Sciences Center of Emory University produced this news release.

Media Relations Contacts: Holly Korschun, Emory University (hkorsch@emory.edu)(404-727-3990) or John Toon, Georgia Tech (jtoon@gatech.edu)(404-894-6986).

At least that's the hope of researchers developing a new method of vaccine delivery that people could even use at home: a patch with microneedles.

Microneedles?

That's right, tiny little needles so small you don't even feel them. Attached to a patch like a Band-Aid, the little needles barely penetrate the skin before they dissolve and release their vaccine.

Researchers led by Mark Prausnitz of Georgia Institute of Technology reported their research on microneedles in Sunday's edition of Nature Medicine.

The business side of the patch feels like fine sandpaper, he said. In tests of microneedles without vaccine, people rated the discomfort at one-tenth to one-twentieth that of getting a standard injection, he said. Nearly everyone said it was painless.

Visit URL below to view full NPR article:

http://www.npr.org/templates/story/story.php?storyId=128603588

The patch does away with needles and syringes and could transform the battle against future pandemics by painlessly inoculating patients with vaccines that could be sent out in the post and self-administered in the home by somebody with no medical experience.

In the developing world, the skin patches could eliminate the need for the costly medical infrastructure of mass-vaccination campaigns, which require trained medical personnel to inject vaccines, and expensive storage equipment. Skin patches also bypass the hazards of dirty needles.

The skin patch is "armed" with an array of microscopic needles made of biodegradable plastic that painlessly scratch the surface of the skin and dissolve harmlessly without trace after delivering the vaccine safely inside the body.

To view full article, visit URL below:

http://www.independent.co.uk/news/science/patch-heralds-new-era-in-battl...

It's enough to make a kid scream. A shot can be an unpleasant experience for anyone, no matter the age. Funding by government flu grants, researchers at Georgia Tech and Emory University in Atlanta developed a solution - needles so small, you can't feel them. It's as long as one or a few hairs are thick, said Georgia Tech researcher, Mark Prausnitz. They're called microneedles, so tiny they only go part of the way through the skin, just deep enough to work but not enough to hit nerves and actually hurt. Research shows microneedles might be more effective than traditional shots, and perhaps the biggest advantage, they're so simple, people can vaccinate themselves. If all goes well, researchers say in five years, microneedles could make doctors' visits a little more pain-free. Brooke Baldwin, CNN, Atlanta. To view the segment, go to following link to open file: CNN Video

To view Georgia Tech article: Flu Vaccine Given In Microneedle Patches

View full article

Visit Prausnitz lab

Recipients of this honor are recognized for their outstanding achievements in medical and biological engineering. A formal induction ceremony will be held during the Institute's Annual Event at the National Academy of Sciences building in Washington, D.C. on February 11-13, 2009.

ABOUT DR. MARK PRAUSNITZ
Dr. Prausnitz and his colleagues carry out research on biophysical methods of drug delivery using ultrasound, microneedles and other approaches. The success of drug and gene delivery is limited by the inability of drugs, proteins and DNA to cross biological barriers in the body. The most daunting barrier is that posed by lipid bilayers, which block transport into cells, into tissues, and into the body. The Prausnitz lab studies the effect of ultrasound and microneedles to selectively and reversibly disrupt those biological barriers and thereby deliver drugs into the body across the skin, into the eye, and into targeted cells through short-lived holes their membranes. Ultrasound studies focus on the mechanisms by which ultrasound disrupts membranes and drives intracellular delivery of molecules, as well as mechanisms of cell death. Microneedles studies address basic questions of drug transport, avoidance of pain, and insertion mechanics of microneedles in skin along with applied questions relating to drug and vaccine delivery and needle fabrication technologies. Additional studies address electroporation for drug and gene delivery, pore-forming peptides for transdermal delivery, theoretical and experimental studies of drug delivery to the eye, and enhanced transfection of plant cells for forestry biotechnology.

In addition to training graduate students in the laboratory, Dr. Prausnitz is actively involved with teaching undergraduate students in the classroom. His core courses are introductory classes on mass and energy balances and thermodynamics and the upper-division course on unit operations laboratory. An elective course developed by Dr. Prausnitz is entitled "Effective Communication for Professional Engineering," which addresses oral and written communication in the context of a case study of the nicotine patch.

Another elective course, developed in collaboration with Dr. Bommarius, is entitled "Drug Design, Development, and Delivery." This course for senior undergraduates and graduate students exposes students to the interplay between multiple technical, as well as economic and societal factors that influence the creation of a successful pharmaceutical.

Dr. Prausnitz has co-authored more than 100 research articles, given 120 invited lectures to industry and academia, published 170 conference abstracts, holds close to 20 issued or pending patents, and has served as an expert witness. Among his honors are the NSF/NIH Scholar-in-Residence at the National Institutes of Health, CAREER Young Investigator Award from the National Science Foundation, TR100 Young Innovator Award from Technology Review and Young Investigator Award and Outstanding Pharmaceutical Paper Award from the Controlled Release Society.

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Kelly Marie Boyd doesn't do well when waiting to get a shot.

"I will start feeling faint, feeling nauseated before they even walk into the room. If I see a needle, I will pass out," she said. With a little girl on the way, she dreads having to put her baby through childhood vaccinations.

A new invention may help make things less terrifying for Kelly and others like her. The new tool could eliminate a need for needles, by using what's called a transdermal patch.

"That way you can put the drug on the skin. It sits there for a period of time and the drug makes its way across the skin," said Dr. Mark Prausnitz of Georgia Institute of Technology.

The "microneedles" work just like a nicotine patch, but use - you guessed it - microscopic needles. "So small that on the one hand, you don't feel them. Probably you don't even see them," Prausnitz said.

On the other hand, they're large enough to do what's needed. "The channels that they have are big enough to deliver most any drug or even vaccine that you would like to give," Prausnitz said.

Not only is it less painful, this may also be a more effective way of delivering drugs.

"There is a class of immune cells that live in the very top layer of skin. So, if you can give the vaccine right there at the top layer of skin, you can get a better immune response," Prausnitz said.

With a better response, smaller doses of the drug may be given than what is traditionally needed. You may even be able to use them right at home.

"You just stick it on and you're done," Dr. Prausnitz said.

Researchers hope these microneedles will have a big impact in third-world countries, where there's a huge need for a better way to vaccinate large groups against deadly diseases such as hepatitis B and smallpox.

The funds will support research and development of vaccine-filled microneedles that are designed to dissolve in the skin to provide protection against the poliovirus in humans. Studies with animal models have shown that microneedle patches containing polio vaccine effectively stimulate the immunological responses necessary for immunization.

A Phase I clinical trial funded by the award will evaluate whether the microneedle patches can be safely and effectively used to supplement current immunization efforts, bridging a gap between existing polio vaccines taken orally and those injected with conventional hypodermic needles.

The patches, about an inch square, contain 100 vaccine-filled needles that are about the diameter of a human hair. In use, they are pressed onto the skin, where the needles quickly dissolve to leave only a harmless patch backing with no sharps waste for disposal. The patches can be applied by minimally-trained personnel, facilitating their use in vaccination programs even in remote areas and areas with weaker health systems.

“We believe that the microneedle patch has the potential to help complete the polio eradication effort with a simple-to-administer patch that can be used in immunization efforts in all countries,” said Mark Prausnitz, a Regents Professor in the School of Chemical & Biomolecular Engineering at the Georgia Institute of Technology.

Existing oral polio vaccines are made with a live, attenuated virus. The inexpensive vaccine can be administered house-to-house in mass vaccination campaigns by minimally-trained personnel who place a drop of the vaccine into the mouths of those being vaccinated.

However, the live virus contained in this vaccine can, in very rare cases, mutate to a virulent form. If that happens, individuals being vaccinated with oral polio vaccine can become infected with the virus, meaning the oral vaccine must be phased out after polio has been successfully eradicated. After polio has been eradicated, inactivated polio vaccine will be the only vaccine used worldwide to maintain immunity levels to the disease.

Existing injectable polio vaccines are made with an inactivated form of the virus. Because it is injected, the vaccine must be administered by trained medical personnel. The vaccine itself is considerably more expensive than the oral vaccine. The cost, together with the need for administration in a medical setting, means the inactivated virus is much more difficult to use in mass vaccination campaigns in developing countries.

The microneedle patch uses dissolving needles made from the vaccine based on inactivated virus, which cannot mutate. But unlike the injectable version, the microneedle version could be applied by minimally-trained personnel, thereby facilitating use in developing countries.

“This new vaccine technology has the potential to significantly increase reach to children everywhere, including in the most marginalized areas of the world. Because it does not need to be injected means achieving high vaccination coverage would be significantly easier, and this is crucial, particularly in outbreak situations,” commented Dr. Roland Sutter, coordinator of Research and Product Development, Polio Operations, for the World Health Organization (WHO).

The researchers funded by these Gates Foundation awards will be developing methods to reduce the cost of manufacturing the microneedle patch vaccine. Studies have shown that injections into the skin using a hypodermic needle or a jet injector can prompt the desired immunological response with smaller amounts of vaccine than is required for a traditional intramuscular injection. Determining the minimum level of vaccine needed in microneedle patches will be one goal for the new research.

Laboratory studies of microneedle vaccine patches have already shown the vaccine to be stable during manufacturing, and additional research will be done to develop patch designs that are stable during long-term storage without refrigeration. Eliminating the need for cold storage could reduce logistical costs.

In the first year of the two-year project, Georgia Tech researchers will develop the formulation to be used in the patches and prepare the technology for manufacturing by Micron Biomedical.

“The grant has a clear goal: At the end of the first year, we have to be able to show compelling data that we’ve made a patch that can do what it needs to do,” said Prausnitz. “Georgia Tech will then hand off the patch design to the company for clinical trials on the vaccine’s safety and immunogenicity during the second year.”

The vaccine patch will likely be about the size of a postage stamp, including an area in the center where the microneedles are located. The tiny needles – too small to be seen with the unaided eye – will be surrounded by an area of adhesive designed to keep the patch on the skin of the person being vaccinated. In addition to the vaccine, the needles will include polymer and other materials that have been approved for use in pharmaceutical products.

“The materials in the microneedles are water soluble, so when the patch is pressed into the skin, the needles are designed to dissolve quickly,” explained Prausnitz. “The intent is that after 15 minutes, you can remove the patch and the needles will have dissolved, leaving only a backing that can be discarded.”

The Phase I clinical trial for the polio vaccine patch may be followed by a second phase, or the project may go directly to larger-scale studies. Ultimately, the polio vaccine patch will need to be approved for use by national regulatory authorities.

Development of the vaccine patch began about five years ago, and has also involved funding from the WHO, the Global Immunization Division of the U.S. Centers for Disease Control and Prevention (CDC), and a Grand Challenges Exploration grant from the Gates Foundation.

In a related study, a clinical trial is planned to begin later this year to assess the use of microneedle patches in vaccinating against influenza. The work, being done in collaboration with Emory University, is funded by the National Institutes of Health. Researchers working on the polio vaccine effort believe their project will benefit from what is learned in the influenza project, and that both studies will demonstrate that the microneedle patch technology is ready for use in humans.

Micron Biomedical (www.micronbiomedical.com) is commercializing a novel vaccine and drug delivery technology, based on dissolving microneedle patches and aimed at achieving better health outcomes through enhanced therapeutic efforts, simplified logistics and improved patient compliance.

Mark Prausnitz is an inventor of patents that have been or may be licensed to companies developing microneedle-based products, is a paid advisor to companies developing microneedle-based products, and is a founder/shareholder of companies developing microneedle-based products, including Micron Biomedical. The resulting potential conflict of interest has been disclosed and is managed by the Georgia Institute of Technology and Emory University.

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Media Relations Contacts: John Toon (404-894-6986) (jtoon@gatech.edu) or Brett Israel (404-385-1933) (brett.israel@comm.gatech.edu).
Writer: John Toon

The grants to Georgia Tech and Micron Biomedical will support research and development of vaccine-filled microneedles that are designed to dissolve in the skin to provide protection against the poliovirus in humans. Studies with animal models have shown that microneedle patches containing polio vaccine effectively stimulate the immunological responses necessary for immunization.

A Phase I clinical trial funded by the award will evaluate whether the microneedle patches can be safely and effectively used to supplement current immunization efforts, bridging a gap between existing polio vaccines taken orally and those injected with conventional hypodermic needles.

The patches, about an inch square, contain 100 vaccine-filled needles that are about the diameter of a human hair. In use, they are pressed onto the skin, where the needles quickly dissolve to leave only a harmless patch backing with no sharps waste for disposal. The patches can be applied by minimally trained personnel, facilitating their use in vaccination programs even in remote areas and areas with weaker health systems.

“We believe that the microneedle patch has the potential to help complete the polio eradication effort with a simple-to-administer patch that can be used in immunization efforts in all countries,” Prausnitz said.

Existing oral polio vaccines are made with a live, attenuated virus. The inexpensive vaccine can be administered house-to-house in mass vaccination campaigns by minimally-trained personnel who place a drop of the vaccine into the mouths of those being vaccinated.

However, the live virus contained in this vaccine can, in very rare cases, mutate to a virulent form. If that happens, individuals being vaccinated with oral polio vaccine can become infected with the virus, meaning the oral vaccine must be phased out after polio has been successfully eradicated. After polio has been eradicated, inactivated polio vaccine will be the only vaccine used worldwide to maintain immunity levels to the disease.

Existing injectable polio vaccines are made with an inactivated form of the virus. Because it is injected, the vaccine must be administered by trained medical personnel. The vaccine itself is considerably more expensive than the oral vaccine. The cost, together with the need for administration in a medical setting, means the inactivated virus is much more difficult to use in mass vaccination campaigns in developing countries.

The microneedle patch uses dissolving needles made from the vaccine based on inactivated virus, which cannot mutate. But unlike the injectable version, the microneedle version could be applied by minimally-trained personnel, thereby facilitating use in developing countries.

“This new vaccine technology has the potential to significantly increase reach to children everywhere, including in the most marginalized areas of the world. Because it does not need to be injected means achieving high vaccination coverage would be significantly easier, and this is crucial, particularly in outbreak situations,” commented Dr. Roland Sutter, coordinator of Research and Product Development, Polio Operations, for the World Health Organization (WHO).

The researchers funded by these Gates Foundation awards will be developing methods to reduce the cost of manufacturing the microneedle patch vaccine. Studies have shown that injections into the skin using a hypodermic needle or a jet injector can prompt the desired immunological response with smaller amounts of vaccine than is required for a traditional intramuscular injection. Determining the minimum level of vaccine needed in microneedle patches will be one goal for the new research.

Laboratory studies of microneedle vaccine patches have already shown the vaccine to be stable during manufacturing, and additional research will be done to develop patch designs that are stable during long-term storage without refrigeration. Eliminating the need for cold storage could reduce logistical costs.

In the first year of the two-year project, Georgia Tech researchers will develop the formulation to be used in the patches and prepare the technology for manufacturing by Micron Biomedical.

“The grant has a clear goal: At the end of the first year, we have to be able to show compelling data that we’ve made a patch that can do what it needs to do,” said Prausnitz. “Georgia Tech will then hand off the patch design to the company for clinical trials on the vaccine’s safety and immunogenicity during the second year.”

The vaccine patch will likely be about the size of a postage stamp, including an area in the center where the microneedles are located. The tiny needles – too small to be seen with the unaided eye – will be surrounded by an area of adhesive designed to keep the patch on the skin of the person being vaccinated. In addition to the vaccine, the needles will include polymer and other materials that have been approved for use in pharmaceutical products.

“The materials in the microneedles are water soluble, so when the patch is pressed into the skin, the needles are designed to dissolve quickly,” explained Prausnitz. “The intent is that after 15 minutes, you can remove the patch and the needles will have dissolved, leaving only a backing that can be discarded.”

The Phase I clinical trial for the polio vaccine patch may be followed by a second phase, or the project may go directly to larger-scale studies. Ultimately, the polio vaccine patch will need to be approved for use by national regulatory authorities.

Development of the vaccine patch began about five years ago, and has also involved funding from the WHO, the Global Immunization Division of the U.S. Centers for Disease Control and Prevention (CDC), and a Grand Challenges Exploration grant from the Gates Foundation.

In a related study, a clinical trial is planned to begin later this year to assess the use of microneedle patches in vaccinating against influenza. The work, being done in collaboration with Emory University, is funded by the National Institutes of Health. Researchers working on the polio vaccine effort believe their project will benefit from what is learned in the influenza project, and that both studies will demonstrate that the microneedle patch technology is ready for use in humans.

Micron Biomedical is commercializing a novel vaccine and drug delivery technology, based on dissolving microneedle patches and aimed at achieving better health outcomes through enhanced therapeutic efforts, simplified logistics and improved patient compliance.

Mark Prausnitz is an inventor of patents that have been or may be licensed to companies developing microneedle-based products, is a paid advisor to companies developing microneedle-based products, and is a founder/shareholder of companies developing microneedle-based products, including Micron Biomedical. The resulting potential conflict of interest has been disclosed and is managed by the Georgia Institute of Technology and Emory University.

Story by John Toon. Courtesy of Research News at Georgia Institute of Technology.