Chemotherapeutic potential of alginate-chitosan microspheres as anti-tubercular drug carriers.
OBJECTIVE
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.


CONCLUSIONS
Alginate-chitosan microspheres hold promise as a potential natural polymer-based oral ATD carrier for better management of TB.
Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh-160 012, India.
Rajesh
R
Pandey
G K
GK
Khuller
D000464:Alginates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002686:Chitin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D048271:Chitosan; D004337:Drug Carriers; D005260:Female; D020723:Glucuronic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006168:Guinea Pigs; D006603:Hexuronic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008863:Microspheres; D014018:Tissue Distribution / Q000502:physiology; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
D000464:Alginates; D000995:Antitubercular Agents; D004337:Drug Carriers; D006603:Hexuronic Acids; D002686:Chitin; D020723:Glucuronic Acid; D048271:Chitosan