JAC Advance Access originally published online on March 3, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 635-640
© 2004 The British Society for Antimicrobial Chemotherapy
Chemotherapeutic potential of alginate–chitosan microspheres as anti-tubercular drug carriers
Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh—160 012, India
Received 3 November 2003; returned 8 December 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
* Corresponding author. Tel: +91-172-747-585, ext. 5174/75; Fax: +91-172-744-401, 745-078; E-mail: gkkhuller{at}yahoo.co.in
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