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JAC Advance Access published online on May 5, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh260
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received February 10, 2004
Revised March 26, 2004
Accepted April 6, 2004

Brief report

Subcutaneous nanoparticle-based antitubercular chemotherapy in an experimental model

Rajesh Pandey 1 G. K. Khuller 1*

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

* To whom correspondence should be addressed. E-mail: gkkhuller{at}yahoo.co.in.


  Abstract

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.

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


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