The long-term objective of this project is to develop a novel treatment for drug abuse. Buprenorphine is a highly lipophilic partial mu-opiate agonist, which is being tested for opiate maintenance program. In order to provide long-term constant buprenorphine delivery, it is desirable to develop a sustained release formulation, which could be implanted subcutaneously. In order to deliver buprenorphine at a constant rate over a prolonged period, we propose to develop sustained release microcapsules. We hypothesize that subcutaneous administration of buprenorphine microcapsules will deliver long-term therapeutic plasma concentrations of buprenorphine.
The specific aims of this proposal are to: (1) develop sustained release microcapsules of buprenorphine, (2) evaluate in vitro drug release characteristics of the microcapsules, (3) evaluate in vivo performance of the microcapsules, and (4) evaluate the long-term stability of the microcapsules. Buprenorphine microcapsules will be prepared using poly(lactide-co-glycolide) by a novel microencapsulation technique. This unique microencapsulation technique has been developed in the PI's laboratory, where the active ingredients are incorporated within a hydrogel followed by microencapsulation within a synthetic biodegradable polymer. Preliminary experiments just completed in our laboratory revealed that the use of a crosslinked hydrogel, before the microencapsulation, could significantly increase the drug loading. It also revealed that the drug was present within the hydrogel in the dissolved state. As a result, incorporation of the hydrogel significantly reduced the burst effect and overall dissoluation of the drug. The buprenorphine microcapsules will be tested in rabbits for in vivo release and biocompatibility. The microcapsules will also be tested in a rat model for agonist effect and heroin dose effect. Following the successful preclinical evaluations in rabbits and rats, this novel delivery system can be used, in the future, for evaluation in monkeys followed by human clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15DA013512-01A2
Application #
6555563
Study Section
Pharmacology A Study Section (PHRA)
Program Officer
Park, Moo Kwang
Project Start
2002-09-30
Project End
2006-08-31
Budget Start
2002-09-30
Budget End
2006-08-31
Support Year
1
Fiscal Year
2002
Total Cost
$68,113
Indirect Cost
Name
Xavier University of Louisiana
Department
Other Health Professions
Type
Schools of Pharmacy
DUNS #
020857876
City
New Orleans
State
LA
Country
United States
Zip Code
70125
Graves, Richard A; Poole, Daniel; Moiseyev, Raisa et al. (2008) Encapsulation of indomethacin using coaxial ultrasonic atomization followed by solvent evaporation. Drug Dev Ind Pharm 34:419-26
Pamujula, Sarala; Graves, Richard A; Moiseyev, Raisa et al. (2008) Preparation of polylactide-co-glycolide and chitosan hybrid microcapsules of amifostine using coaxial ultrasonic atomizer with solvent evaporation. J Pharm Pharmacol 60:283-9
Praetorius, Natalie P; Mandal, Tarun K (2007) Engineered nanoparticles in cancer therapy. Recent Pat Drug Deliv Formul 1:37-51
Graves, Richard A; Freeman, Thomas; Mandal, Tarun K (2007) In vitro dissolution method for evaluation of buprenorphine in situ gel formulation: a technical note. AAPS PharmSciTech 8:E62
Graves, Richard A; Freeman, Thomas; Pamajula, Sarala et al. (2006) Effect of co-solvents on the characteristics of enkephalin microcapsules. J Biomater Sci Polym Ed 17:709-20
Graves, Richard A; Moiseyev, Raisa; Freeman, Thomas et al. (2005) Effect of surfactant on the characteristics of biodegradable microcapsules. J Biomater Sci Polym Ed 16:585-96
Graves, Richard A; Pamujula, Sarala; Moiseyev, Raisa et al. (2004) Effect of different ratios of high and low molecular weight PLGA blend on the characteristics of pentamidine microcapsules. Int J Pharm 270:251-62