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JAC Advance Access originally published online on May 5, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(1):266-268; doi:10.1093/jac/dkh260
JAC vol.54 no.1 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.

Subcutaneous nanoparticle-based antitubercular chemotherapy in an experimental model

Rajesh Pandey and G. K. Khuller*

Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh-160 012, India

* Corresponding author. Tel: +91-172-2747585, ext. 5174-75; Fax: +91-172-2744401, 2745078; Email: gkkhuller{at}yahoo.co.in

Poly (DL-lactide-co-glycolide) (PLG) nanoparticles encapsulating three front-line antitubercular drugs, i.e. rifampicin, isoniazid and pyrazinamide, were prepared by the multiple emulsion technique and administered subcutaneously to mice for pharmacokinetic/chemotherapeutic study. A single subcutaneous dose of drug-loaded PLG nanoparticles resulted in sustained therapeutic drug levels in the plasma for 32 days and in the lungs/spleen for 36 days. The mean residence time and absolute bioavailability were increased several-fold as compared with unencapsulated drugs. Further, drug-loaded PLG nanoparticles resulted in undetectable bacterial counts in the lungs and spleen of Mycobacterium tuberculosis-infected mice, thereby demonstrating a better chemotherapeutic efficacy, as compared with daily free drug treatment. Hence, injectable PLG nanoparticles hold promise for increasing drug bioavailability and reducing dosing frequency for better management of tuberculosis.

Keywords: poly (DL-lactide-co-glycolide) , tuberculosis , bioavailability


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