JAC Advance Access originally published online on August 25, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(4):761-766; doi:10.1093/jac/dkh411
JAC vol.54 no.4 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved
Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolized antitubercular drug carriers for treatment of tuberculosis
Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh–160 012, India
* Corresponding author. Tel: +91-172-2747585, ext. 5174-75; Fax: +91-172-2744401/+91-172-2745078; Email: gkkhuller{at}yahoo.co.in
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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