It is well known that the method by which a drug is delivered can have a significant effect on the drug's therapeutic efficacy. Most drugs have a concentration range in which they have maximum efficacy. Conventional drug delivery regimens result in sharp changes in systemic drug levels that can be fatal. Controlled drug delivery can alleviate the problems associated with conventional therapy by providing stable drug bioavailability in a therapeutically meaningful range and in addition can be used to localize the therapy to the tissue site of interest. We recently showed that it is possible to fabricate a solid-state silicon microchip in which a number of chemicals or drugs can be stored and released on demand by an external trigger. One advantage of this novel controlled release system is that it allows for simultaneous release of multiple drugs in complex release profiles. One can potentially develop a device that can be pre- programmed to delivery combination drugs in a pre-determined fashion. We believe that this novel delivery technology has broad utility in the biomedical area such as local delivery of anesthetics for pain management, sub-dermal delivery of vaccines, periodontal delivery of antibiotic and anti-inflammatory agents, localized delivery of anti-tumor and neoplastic agents, gene delivery, delivery of antiarrhythmic agents to name a few. Based on the above mentioned rationale and our preliminary results we propose the following specific aims: (1) Development of an active, silicon based microchip for controlled release of drugs that can operate autonomously, (2) Development of a passive, polymeric chip for the controlled release of drugs, (3) Evaluate the biocompatibility of active and passive microchip delivery device and (4) Evaluate the drug release both in vitro and in vivo, specifically: (a) show that predictable drug release is possible from both active and passive microchips (b) study a pathology such as brain tumors that maybe be better treated by combination therapy (c) evaluate the efficacy of these devices in this tumor model.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Resource-Related Research Projects (R24)
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Special Emphasis Panel (ZRG1-SSS-Z (03))
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Gondre-Lewis, Timothy A
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Massachusetts Institute of Technology
Engineering (All Types)
Schools of Engineering
United States
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