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JAC Advance Access published online on August 25, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh411
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received May 25, 2004
Revised July 20, 2004
Accepted July 22, 2004

Original article

Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolized antitubercular drug carriers for treatment of tuberculosis

Anjali Sharma 1, Sadhna Sharma 1, G. K. Khuller 1*

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

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


  Abstract

Objectives: This study was carried out to explore lectin-functionalized poly (lactide-co-glycolide) nanoparticles (PLG-NPs) as bioadhesive drug carriers against tuberculosis (TB), in order to reduce the drug dosage frequency of antitubercular drugs and thus improve patient compliance in TB chemotherapy.

Methods: Wheat germ agglutinin (WGA)-coated PLG-NPs were prepared by a two-step carbodiimide procedure. This formulation was administered to guinea pigs through the oral/aerosol route for a detailed pharmacokinetic and chemotherapeutic evaluation. Immunological or hepatotoxic effects of WGA lectin, if any, were also determined.

Results: WGA-functionalized PLG-NPs were in the size range of 350-400 nm, with binding of 3-3.5 µg of WGA/mg of PLG-NPs and drug encapsulation efficiency of 54%-66%. Upon administration of lectin-coated PLG-NPs through the oral/aerosol route, the presence of drugs in plasma was observed for 6-7 days for rifampicin and 13-14 days for isoniazid and pyrazinamide. However, upon administration of uncoated PLG-NPs (oral/aerosolized) rifampicin was detectable in plasma for 4-6 days, whereas isoniazid and pyrazinamide were detectable for 8-9 days. All three drugs were present in lungs, liver and spleen for 15 days. Administration of WGA-coated PLG-NPs caused a significant (P < 0.001) increase in the relative bioavailability of antitubercular drugs. Chemotherapeutic studies revealed that three doses of oral/nebulized lectin-coated nanoparticles fortnightly could yield undetectable mycobacterial colony forming units (cfu); this was achievable with 45 doses of oral free drugs.

Conclusion: WGA-functionalized PLG-NPs could be potential drug carriers for antitubercular drugs through the oral as well as aerosol route for effective TB control.

Keywords: polymers; pharmacokinetics; bioavailability; drug delivery.
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