Improved pharmacotherapies for the opioid addiction treatment are needed to maintain addicts in treatment for extended periods. Development of a novel drug delivery system will also keep the addicts away from high-risk tuberculosis and HIV/AIDS transmission associated with the intravenous drug abuse. One of the current treatments for opioid addiction is to use opioid agonists and/or antagonists, which generally have chemical structures similar to those of opioid. One such opioid substitution agent on the treatment horizon is structures similar to those of opioid. One such opioid substitution agent on the treatment horizon is buprenorphine. Currently, sublingual administration of buprenorphine is an investigational pharmacotherapy for the treatment of opioid addiction. However, a sustained release preparation of buprenorphine will have an advantage over current dosage forms, which require dosing daily or three times a week. Thus, the development of a novel drug delivery system of buprenorphine capable of maintaining a therapeutically useful plasma concentration over an extended period is recognized as an important area of research. In order to delivery buprenorphine at a constant rate over a prolonged period, we proposed to develop biodegradable implant systems. These implant systems will include i) biodegradable microcapsules, and ii) in situ polymeric gel. These implant systems will be developed using several grades of poly(lactide-co-glycolide) and poly(caprolactone). The first delivery system, sustained release microcapsules, will be prepared by a novel biodegradable polymers in a water miscible biocompatible solvent, e.g., N-methyl-2- pyrrolidone, dimethyl sulfoxide, ethyl acetate, acetone, ethanol, and propylene glycol. This polymer solution containing buprenorphine will be injected into the body. The water miscible solvent will diffuse from the site of infection and water will permeate into the polymer matrix resulting in a solid implant. Buprenorphine, encapsulated into polymer matrix, will release slowly over an extended period. Following the preparation, these delivery systems will be evaluated for physicochemical characteristics. These preparations will be tested in rats for preclinical evaluations, which include pharmacokinetic studies and biological compatibility studies, Following the successful preclinical evaluations, these novel delivery systems can be used, in the future, for clinical trials. Thus, the development of these novel delivery systems will bring a new pharmacotherapy for opioid addiction treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Resource-Related Research Projects (R24)
Project #
2R24DA007970-07A1
Application #
6201588
Study Section
Project Start
1999-08-01
Project End
2000-05-31
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Xavier University of Louisiana
Department
Type
DUNS #
020857876
City
New Orleans
State
LA
Country
United States
Zip Code
70125
Mayence, Annie; Vanden Eynde, Jean Jacques; Krogstad, Fran M et al. (2004) Parallel solution-phase synthesis of conformationally restricted congeners of pentamidine and evaluation of their antiplasmodial activities. J Med Chem 47:2700-5
Mayence, Annie; Vanden Eynde, Jean Jacques; LeCour Jr, Louis et al. (2004) Piperazine-linked bisbenzamidines: a novel class of antileishmanial agents. Eur J Med Chem 39:547-53
Homayoun, P; Mandal, T; Landry, D et al. (2003) Controlled release of anti-cocaine catalytic antibody from biodegradable polymer microspheres. J Pharm Pharmacol 55:933-8
Donkor, Isaac O; Huang, Tien L; Tao, Bin et al. (2003) Trypanocidal activity of conformationally restricted pentamidine congeners. J Med Chem 46:1041-8
Mandal, Tarun K; Bostanian, Levon A; Graves, Richard A et al. (2002) Poly(D,L-lactide-co-glycolide) encapsulated poly(vinyl alcohol) hydrogel as a drug delivery system. Pharm Res 19:1713-9
Zhang, Qiang; Ma, Peng; Iszard, Marcus et al. (2002) In vitro metabolism of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate, a cannabinoid receptor agonist. Drug Metab Dispos 30:1077-86
Brakta, Mohamed; Murthy, Devangachinta; Ellis, L'Ouverture et al. (2002) 9-[(Hydroxymethyl)phenyl]adenines: new aryladenine substrates of adenosine deaminase. Bioorg Med Chem Lett 12:1489-92
Huang, T L; Tao, B; Quarshie, Y et al. (2001) N,N'-bis[4-(N-alkylamidino)phenyl]homopiperazines as anti-Pneumocystis carinii agents. Bioorg Med Chem Lett 11:2679-81
Mandal, T K; Bostanian, L A (2000) Effect of peptide loading and surfactant concentration on the characteristics of physically crosslinked hydrogel. Pharm Dev Technol 5:555-60
Mandal, T K (2000) Swelling-controlled release system for the vaginal delivery of miconazole. Eur J Pharm Biopharm 50:337-43

Showing the most recent 10 out of 17 publications