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JAC Advance Access published online on March 13, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg165
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

Alginate-based oral drug delivery system for tuberculosis: pharmacokinetics and therapeutic effects

Qurrat-ul- Ain 1, Sadhna Sharma 1, G. K. Khuller 1*, S. K. Garg 2

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

* Corresponding author. E-mail: gkkhuller{at}yahoo.co.nic.in.

Received 20 August 2002 ; revised 27 October 2002 ; accepted 20 January 2003

Abstract

Alginate microparticles were developed as oral sustained delivery carriers for antitubercular drugs in order to improve patient compliance. In the present study, pharmacokinetics and therapeutic effects of alginate microparticle encapsulated antitubercular drugs, i.e. isoniazid, rifampicin and pyrazinamide were examined in guinea pigs. Alginate microparticles containing antitubercular drugs were evaluated for in vitro and in vivo release profiles. These microparticles exhibited sustained release of isoniazid, rifampicin and pyrazinamide for 3-5 days in plasma and up to 9 days in organs. Peak plasma concentration (Cmax), Tmax, elimination half-life (t1/2e) and AUC0-{infty} of alginate drugs were significantly higher than those of free drugs. The encapsulation of drug in alginate microparticles resulted in up to a nine-fold increase in relative bioavailability compared with free drugs. Chemotherapeutic efficacy of alginate drug microspheres against experimental tuberculosis showed no detectable cfu values at 1:100 and 1:1000 dilutions of spleen and lung homogenates. Histopathological studies further substantiated these observations, thus suggesting that application of alginate-encapsulated drugs could be useful in the effective treatment of tuberculosis.

Keywords: tuberculosis, pharmacokinetics, alginate, drug delivery, antitubercular drugs
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