JAC Advance Access published online on March 3, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh139
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Biochemistry, Postgraduate Institute of Medical
Education & Research,
Chandigarh--160 012, India
* Corresponding author. E-mail: gkkhuller{at}yahoo.co.in.
Received 3 November 2003
; revised 17 December 2003
; accepted 6 January 2004
Objectives: This study was designed
to develop alginate-chitosan microspheres as drug carriers
to reduce dose/dosing frequency in the management of tuberculosis
(TB), which otherwise demands prolonged chemotherapy. Methods: Alginate-chitosan microspheres
encapsulating three frontline anti-tuberculous drugs (ATDs), rifampicin,
isoniazid and pyrazinamide, were formulated. A therapeutic dose
and a half-therapeutic dose of the microsphere-encapsulated ATDs
were orally administered to guinea pigs for pharmacokinetic/chemotherapeutic
evaluations, respectively. Results: The drug encapsulation efficiency ranged
from 65% to 85% with a loading of 220-280
mg of drug per gram microspheres. Administration of a single oral
dose of the microspheres to guinea pigs resulted in sustained drug
levels in the plasma for 7 days and in the organs for 9 days. The
half-life and mean residence time of the drugs were increased 13-
to 15-fold by microsphere encapsulation, along with an enhanced relative/absolute
bioavailability. The sustained release and increase in bioavailability
were also observed with a sub-therapeutic dose of the microspheres.
In Mycobacterium tuberculosis H37Rv-infected
guinea pigs, administration of a therapeutic dose of microspheres
spaced 10 days apart produced a clearance of bacilli equivalent
to conventional treatment for 6 weeks. The most important observation,
however, was the documentation of therapeutic benefit with a half-therapeutic
dose of the microspheres administered weekly. Conclusion: Alginate-chitosan microspheres
hold promise as a potential natural polymer-based oral ATD carrier
for better management of TB.
Keywords: tuberculosis, polymers, bioavailability, chemotherapy
Chemotherapeutic potential of alginate-chitosan
microspheres as
anti-tubercular drug carriers
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