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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Resource-Related Research Projects (R24)
Project #
5R24AI047739-03
Application #
6374541
Study Section
Special Emphasis Panel (ZRG1-SSS-Z (03))
Program Officer
Deckhut Augustine, Alison M
Project Start
1999-09-30
Project End
2004-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
3
Fiscal Year
2001
Total Cost
$899,016
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Lipski, Anna M; Pino, Christopher J; Haselton, Frederick R et al. (2008) The effect of silica nanoparticle-modified surfaces on cell morphology, cytoskeletal organization and function. Biomaterials 29:3836-46
Kim, Grace Y; Tyler, Betty M; Tupper, Malinda M et al. (2007) Resorbable polymer microchips releasing BCNU inhibit tumor growth in the rat 9L flank model. J Control Release 123:172-8
Sussman, Eric M; Clarke Jr, Michael B; Shastri, V Prasad (2007) Single-step process to produce surface-functionalized polymeric nanoparticles. Langmuir 23:12275-9
Xu, Xiao-Jun; Sy, Jay C; Prasad Shastri, V (2006) Towards developing surface eroding poly(alpha-hydroxy acids). Biomaterials 27:3021-30
Daxini, Sachin C; Nichol, Jason W; Sieminski, Alisha L et al. (2006) Micropatterned polymer surfaces improve retention of endothelial cells exposed to flow-induced shear stress. Biorheology 43:45-55
Li, Yawen; Ho Duc, Hong Linh; Tyler, Betty et al. (2005) In vivo delivery of BCNU from a MEMS device to a tumor model. J Control Release 106:138-45
Grayson, Amy C Richards; Cima, Michael J; Langer, Robert (2005) Size and temperature effects on poly(lactic-co-glycolic acid) degradation and microreservoir device performance. Biomaterials 26:2137-45
Li, Yawen; Shawgo, Rebecca S; Tyler, Betty et al. (2004) In vivo release from a drug delivery MEMS device. J Control Release 100:211-9
Richards Grayson, Amy C; Cima, Michael J; Langer, Robert (2004) Molecular release from a polymeric microreservoir device: Influence of chemistry, polymer swelling, and loading on device performance. J Biomed Mater Res A 69:502-12
Grayson, Amy C R; Voskerician, Gabriela; Lynn, Aaron et al. (2004) Differential degradation rates in vivo and in vitro of biocompatible poly(lactic acid) and poly(glycolic acid) homo- and co-polymers for a polymeric drug-delivery microchip. J Biomater Sci Polym Ed 15:1281-304

Showing the most recent 10 out of 17 publications