{"73145":{"#nid":"73145","#data":{"type":"news","title":"New Polymer Shows Promise for Drug Delivery","body":[{"value":"\u003Cp\u003EA newly developed family of biodegradable polymers has shown potential for use in intracellular delivery and sustained release of therapeutic drugs to the acidic environments of tumors, inflammatory tissues and intracellular vesicles that hold foreign matter.\u003C\/p\u003E\n\u003Cp\u003EThese polymers have several advantages over existing biodegradable polymers, researchers said. Among them, the polymers - called polyketals - are biodegradable into Food and Drug Administration-approved compounds. Synthesis is a simple and easily customized process. Degradation of the polymer does not produce inflammation-causing acid, but instead generates membrane-permeable products that allow all of the polymer\u0027s byproducts to diffuse outside the cell. That means byproducts shouldn\u0027t accumulate in a patient\u0027s tissue and cause inflammation.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022We\u0027ve known for 20 to 30 years that when cells take up particles, they move them to a part of the cell with a low pH -- about 5.0,\u0022 said Niren Murthy, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University. \u0022Researchers have been able to successfully exploit this process in cell culture and in animal models, but have done so using materials that generated acid degradation products and that hydrolyzed too slowly for chronic use. Thus, there has been very little clinical activity in this area.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EHowever, polyketal nanoparticles use the cell\u0027s acid to hydrolyze into hydrophilic compounds that can release encapsulated therapeutics at an accelerated rate in the acidic environments to which they are targeted, Murthy explained. Also, unlike polyester-based biomaterials, polyketal nanoparticles do not generate acid when they degrade. Researchers don\u0027t know yet whether polyketals will be less inflammatory than current polymers used for drug delivery, but expect to evaluate this response within the next year.\n\u003C\/p\u003E\n\u003Cp\u003EMurthy presented information on the development and potential applications of polyketals March 27 at the 231st American Chemical Society National Meeting in Atlanta. His collaborators are Emory University immunologist Bali Pulendran, University of Rochester physician Robert Pierce, and Georgia Tech graduate students Michael Heffernan and Stephen Yang. Their research -- under way for the past two and a half years -- is funded by the National Institutes of Health and the National Science Foundation. \n\u003C\/p\u003E\n\u003Cp\u003EDevelopment of the polymer was a surprisingly straightforward process, Murthy said. \u0022There is a reaction that is well known in synthetic organic chemistry called the acetal exchange reaction,\u0022 he explained. \u0022We can change this reaction a little bit and use it to make these polymers. It\u0027s normally a reaction used to protect alcohols, but when you make it react with a molecule with two alcohols, it makes this polymer.\u0022 \n\u003C\/p\u003E\n\u003Cp\u003EBecause this chemical process is a simple one, it is feasible for production of the polymer on an industrial scale, potentially making it widely available, Murthy said. \n\u003C\/p\u003E\n\u003Cp\u003E\u0022We have a lot of flexibility in terms of the types of alcohols we incorporate into the polymer,\u0022 he added. \u0022We can tailor the polymer\u0027s hydrolysis rates and mechanical properties, which would broaden its medical applications. For example, in some cases you want drug delivery faster than others. With acute liver failure, you want drug release in one to two days, whereas with arthritis, you want release over one to two months.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EIn addition to its simple synthesis, another advantage of polyketals is their degradation process, which generates membrane-permeable products, Murthy said. \n\u003C\/p\u003E\n\u003Cp\u003E\u0022The problem with using polyesters as drug delivery vehicles is that most of the illnesses being treated are chronic diseases requiring weekly injections, yet polyesters take months to degrade,\u0022 he noted. \u0022Polyketals hydrolyze in a week, diffuse out of the cell and are then excreted outside of the cell.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EResearchers hope to test polyketals in clinical trials within five years if animal model studies show potential. To date, Pierce has done some testing in mice to treat acute liver failure. He injected polyketal nanoparticles in mice, and the polyketals delivered them to the animals\u0027 livers. But researchers don\u0027t know yet whether their system can deliver treatment in vivo. The answer to that question is about a year away, Murthy added.\n\u003C\/p\u003E\n\u003Cp\u003EPotential applications of polyketals include the delivery of anti-oxidants to treat acute liver failure in people who have suffered an alcohol or acetaminophen overdose. In these patients, the liver stops functioning because macrophage cells in the liver create reactive oxygen species. One of the treatments is the delivery of superoxide dismutase, an enzyme that essentially detoxifies superoxide. \n\u003C\/p\u003E\n\u003Cp\u003EOther applications include the use of polyketals in any type of protein-based vaccine, Murthy said, adding that researchers have not yet pursued this possibility. Yet another application is protein delivery for a wide range of therapeutics, including insulin delivery for Type 1 diabetics - alleviating the need for multiple injections.  \n\u003C\/p\u003E\n\u003Cp\u003EIn mid-2005, Georgia Tech, Emory and the University of Rochester filed two provisional patent applications on the polyketal drug delivery system. Murthy noted that a Japanese patent filed in 2001 described the same polymerization process, but used it to make photo resists, rather than a drug delivery system.\n\u003C\/p\u003E\n\u003Cp\u003EResearchers have discussed the start up of a biomedical company based on this technology, but first they must have some compelling data from animal studies. If they pursue commercialization, the process could potentially be done within Emtech Bio, an early-stage biosciences business incubator operated by Emory University and Georgia Tech. \n\u003C\/p\u003E\n\u003Cp\u003E\u003Cstrong\u003EResearch News \u0026amp; Publications Office\u003Cbr \/\u003E\nGeorgia Institute of Technology\u003Cbr \/\u003E\n75 Fifth Street, N.W., Suite 100\u003Cbr \/\u003E\nAtlanta, Georgia 30308 USA \u003C\/strong\u003E\n\u003C\/p\u003E\n\u003Cp\u003E\u003Cstrong\u003EMedia Relations Contacts\u003C\/strong\u003E: Jane Sanders (404-894-2214); E-mail: (\u003Ca href=\u0022mailto:jane.sanders@edi.gatech.edu\u0022\u003Ejane.sanders@edi.gatech.edu\u003C\/a\u003E) or John Toon (404-894-6986); E-mail: (\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E)\n\u003C\/p\u003E\n\u003Cp\u003E\u003Cstrong\u003ETechnical Contacts\u003C\/strong\u003E:\u003Cbr \/\u003E\n1. Niren Murthy, Georgia Tech (404-385-5145); E-mail: (\u003Ca href=\u0022mailto:niren.murthy@bme.gatech.edu\u0022\u003Eniren.murthy@bme.gatech.edu\u003C\/a\u003E)\u003Cbr \/\u003E\n2. Bali Pulendran, Emory University (404-727-8945); E-mail: (\u003Ca href=\u0022mailto:bali.pulendran@emory.edu\u0022\u003Ebali.pulendran@emory.edu\u003C\/a\u003E)\u003Cbr \/\u003E\n3. Robert Pierce, University of Rochester (585-275-1874); E-mail: (\u003Ca href=\u0022mailto:robert_pierce@urmc.rochester.edu\u0022\u003Erobert_pierce@urmc.rochester.edu\u003C\/a\u003E\n\u003C\/p\u003E\n\u003Cp\u003E\u003Cstrong\u003EWriter\u003C\/strong\u003E: Jane Sanders\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Biodegradable polyketals have advantages for intracellular delivery and sustained release"}],"field_summary":[{"value":"A newly developed family of biodegradable polymers has shown potential for use in intracellular delivery and sustained release of therapeutic drugs to the acidic environments of tumors, inflammatory tissues and intracellular vesicles.","format":"limited_html"}],"field_summary_sentence":[{"value":"New materials show promise for drug delivery"}],"uid":"27303","created_gmt":"2006-03-28 01:00:00","changed_gmt":"2016-10-08 03:03:34","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2006-03-28T00:00:00-05:00","iso_date":"2006-03-28T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"73146":{"id":"73146","type":"image","title":"Niren Murthy","body":null,"created":"1449177979","gmt_created":"2015-12-03 21:26:19","changed":"1475894671","gmt_changed":"2016-10-08 02:44:31"},"73147":{"id":"73147","type":"image","title":"Polyketal materials","body":null,"created":"1449177979","gmt_created":"2015-12-03 21:26:19","changed":"1475894671","gmt_changed":"2016-10-08 02:44:31"}},"media_ids":["73146","73147"],"related_links":[{"url":"http:\/\/www.bme.gatech.edu\/","title":"Wallace H. Coulter Department of Biomedical Engineering"},{"url":"http:\/\/www.bme.gatech.edu\/facultystaff\/faculty_record.php?id=58","title":"Niren Murthy"}],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[],"keywords":[],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cstrong\u003EJohn Toon\u003C\/strong\u003E\u003Cbr \/\u003EResearch News \u0026amp; Publications Office\u003Cbr \/\u003E\u003Ca href=\u0022http:\/\/www.gatech.edu\/contact\/index.html?id=jt7\u0022\u003EContact John Toon\u003C\/a\u003E\u003Cbr \/\u003E\u003Cstrong\u003E404-894-6986\u003C\/strong\u003E","format":"limited_html"}],"email":["jtoon@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}