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


CONCLUSIONS
WGA-functionalized PLG-NPs could be potential drug carriers for antitubercular drugs through the oral as well as aerosol route for effective TB control.
Sharma
Anjali
A
Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh-160 012, India.
Sharma
Sadhna
S
Khuller
G K
GK
D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D015169:Colony Count, Microbial; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D036103:Nanotechnology; D011098:Polyglactin 910 / Q000737:chemistry*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D014018:Tissue Distribution; D014376:Tuberculosis / Q000188:drug therapy* / Q000378:metabolism; D014909:Wheat Germ Agglutinins / Q000737:chemistry*
D000336:Aerosols; D000995:Antitubercular Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D014909:Wheat Germ Agglutinins; D011098:Polyglactin 910