Preparation of Polymeric Micelles for use as Carriers of Tuberculostatic Drugs
| Autor: | Daisy N. Sato, Clarice Queico Fujimura Leite, Eiizabeth I. Ferreira, Márcia Guimarães da Silva |
|---|---|
| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP), Instituto Adolfo Lutz (IAL) |
| Rok vydání: | 2007 |
| Předmět: |
isoniazid
pyrazinamide pyrazinamide isoniazid rifampin tuberculostatic prodrugs polymer micelles medicine.drug_class Chemistry tuberculostatic prodrugs Pharmaceutical Science Conjugated system Prodrug Antimycobacterial Combinatorial chemistry Micelle polymer micelles Sudan III chemistry.chemical_compound Dynamic light scattering Critical micelle concentration medicine Organic chemistry Pharmacology (medical) Solubility rifampin |
| Zdroj: | Tropical Journal of Pharmaceutical Research; Vol 6, No 4 (2007); 815-824 Web of Science Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1596-9827 1596-5996 |
| DOI: | 10.4314/tjpr.v6i4.14665 |
| Popis: | Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:02:05Z No. of bitstreams: 1 WOS000253261500004.pdf: 226451 bytes, checksum: 45c4d40b086673eed2c7d185c488ab68 (MD5) Made available in DSpace on 2014-02-26T17:02:05Z (GMT). No. of bitstreams: 1 WOS000253261500004.pdf: 226451 bytes, checksum: 45c4d40b086673eed2c7d185c488ab68 (MD5) Previous issue date: 2007-12-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:24:31Z No. of bitstreams: 1 WOS000253261500004.pdf: 226451 bytes, checksum: 45c4d40b086673eed2c7d185c488ab68 (MD5) Made available in DSpace on 2014-05-20T13:24:31Z (GMT). No. of bitstreams: 1 WOS000253261500004.pdf: 226451 bytes, checksum: 45c4d40b086673eed2c7d185c488ab68 (MD5) Previous issue date: 2007-12-01 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 antimycobacterial 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. UNESP, Fac Ciências Farmaceut, Dept Farm & Med, Araraquara, SP, Brazil Univ São Paulo, Fac Ciências Farmaceut, Dept Farm, BR-09500900 São Paulo, Brazil UNESP, Fac Ciências Farmaceut, Dept Ciências Biol, Araraquara, SP, Brazil Inst Adolfo Lutz Registro, Ribeirao Preto, Brazil UNESP, Fac Ciências Farmaceut, Dept Farm & Med, Araraquara, SP, Brazil UNESP, Fac Ciências Farmaceut, Dept Ciências Biol, Araraquara, SP, Brazil |
| Databáze: | OpenAIRE |
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