Sustained release of isoniazid from a single injectable dose of poly (DL-lactide-co-glycolide) microparticles as a therapeutic approach towards tuberculosis

Drug delivery strategies to achieve a sustained drug release and increased bioavailability involve the use of biodegradable polymeric drug carriers. Poly (DL-lactide-co-glyoolide) (PLG) microparticles were investigated as carriers for isoniazid (INH). In vitro and in vivo release of INH from different formulations of PLG microparticles was examined. In vitro experiments showed a sustained release of INN Lip to 6 days from non-porous microparticles while porous microparticles released INH over 3 days. Both porous and non-porous microparticles released INH in plasma for up to 2 days. Hardened PLG microparticles sustained release of INH for up to 7 weeks both in vitro and in vivo. The concentrations of INH obtained at all times were much higher than the minimum inhibitory concentration (MIC) of INH. Controls injected with free INH showed release of INH in plasma for up to 12 h and in organs for up to 24 h. There was no hepatotoxicity induced as compared with control animals. Taken together these results suggest that PLG-based antitubercular drugs may serve as ideal therapeutic agents for the treatment of tuberculous infections. (C) 2001 Elsevier Science B.V, and International Society of Chemotherapy. All rights reserved.