Skip Navigation



JAC Advance Access published online on April 5, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl128
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
57/6/1146    most recent
dkl128v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Pandey, R.
Right arrow Articles by Khuller, G. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pandey, R.
Right arrow Articles by Khuller, G. K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received December 2, 2005
Accepted March 13, 2006

Original article

Oral nanoparticle-based antituberculosis drug delivery to the brain in an experimental model

Rajesh Pandey 1 and G. K. Khuller 1 *

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

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


  Abstract

Objectives: To evaluate the potential of orally administered poly-lactide-co-glycolide (PLG, a synthetic polymer) nanoparticle encapsulated antituberculosis drugs (ATDs) (rifampicin + isoniazid + pyrazinamide + ethambutol) for cerebral drug delivery in a murine model.

Methods: The formulation was prepared using the multiple emulsion technique and administered orally to mice for biodistribution, pharmacokinetic and chemotherapeutic studies.

Results: A single oral dose of the formulation to mice could maintain sustained drug levels for 5-8 days in the plasma and for 9 days in the brain. There was a significant improvement in the pharmacokinetic parameters such as mean residence time and relative bioavailability as compared with free drugs. The pharmacodynamic parameters such as the ratio of area under the curve to minimum inhibitory concentration (AUC/MIC) and the time up to which MIC levels were maintained in plasma (TMIC) were also improved. In Mycobacterium tuberculosis H37Rv infected mice, five oral doses of the nanoparticle formulation administered every 10th day resulted in undetectable bacilli in the meninges, as assessed on the basis of cfu and histopathology.

Conclusions: Polymeric nanoparticles bear significant potential for ATD delivery to the brain.

Keywords: poly-lactide-co-glycolide; bioavailability; pharmacodynamics; chemotherapy.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.