Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Preparation of Polymeric Micelles for use as Carriers of Tuberculostatic Drugs.

Márcia Silva¹ , Eiizabeth I Ferreira², Clarice Q. F. Leite³, Daisy N Sato⁴

¹Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas, Unesp, Araraquara - SP, Brazil; ²Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, USP, São Paulo - SP, Brazil; ³Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Unesp, Araraquara - SP, Brazil; ⁴Instituto Adolfo Lutz, Ribeirão Preto - SP, Brazil.

For correspondence:- Márcia Silva Email: silvam@fcfar.unesp.br Tel:+0551633016971

Published: 25 December 2007

Citation: Silva M, Ferreira EI, Leite CQ, Sato DN. Preparation of Polymeric Micelles for use as Carriers of Tuberculostatic Drugs.. Trop J Pharm Res 2007; 6(4):815-824 doi: 10.4314/tjpr.v6i4.4

© 2007 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: This paper focuses on the characterization of polymeric micelle-forming tuberculostatic prodrugs and the antimycobacterial activity of these prodrugs.

Method: By the condensation of hydroxymethylpyrazinamide, isoniazid and rifampin with free carboxyl groups on the copolymer poly(ethyleneglycol)-poly(aspartic acid), micelle-forming carrier-drug conjugates were obtained. These micelles were characterized by dynamic light scattering, to measure the micelle diameter; by acid-base titration, to determine the percentage of carboxylic groups occupied by the tuberculostatic; by Sudan III solubility tests, to estimate the critical micelle concentration (CMC); and visual control and spectrophotometric measurement, to determine the stability of micelles. These micelles were tested in vitro against several Mycobacterium strains.

Results: As expected, the size and distribution of the micelle-forming tuberculostatic prodrugs found to be small (78.2nm, 84.2nm and 98.9 nm) while the level of the drug conjugated was high (65.02-85.7%). Furthermore, the micelles were stable in vitro, exhibiting a low level of CMC and stronger anti-mycobacterial activity than the original drugs.

Conclusion: The results demonstrate that polymeric micelles can be used as efficient carriers for drugs, which alone, exhibit undesired pharmacokinetics, poor solubility, and low stability. The synthesized micelle-forming tuberculostatic prodrugs opens a perspective of alternative prodrugs that prolong action and decrease the toxicity of the tuberculostatic drugs of choice.

Keywords: pyrazinamide, isoniazid, rifampin, tuberculostatic prodrugs, polymer micelles.