Nanoparticle encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis.
Patient non-compliance is the major drawback associated with the long-duration chemotherapy of tuberculosis (TB); hence, reduction in dosing frequency forms an important therapeutic strategy. The present study reports the formulation of three frontline antitubercular drugs (ATD), i.e. rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) encapsulated in poly (DL-lactide-co-glycolide) (PLG) nanoparticles. Drug encapsulation efficiencies were 56.9+/-2.7% for RIF, 66.3+/-5.8% for INH and 68+/-5.6% for PZA. Following a single oral administration of these preparations to mice, the drugs could be detected in the circulation for 6 days (RIF) and 9 days (INH/PZA), whereas therapeutic concentrations in the tissues were maintained for 9-11 days. Further, on oral administration of drug-loaded nanoparticles to Mycobacterium tuberculosis-infected mice at every 10th day, no tubercle bacilli could be detected in the tissues after 5 oral doses of treatment. Therefore, nanoparticle-based ATD therapy forms a sound basis for reduction in dosing frequency for better management of TB.
Pandey
Rajesh
R
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India.
Zahoor
A
A
Sharma
Sadhna
S
Khuller
G K
GK
D000284:Administration, Oral; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods; D005260:Female; D006016:Glycolates; D007538:Isoniazid / Q000008:administration & dosage / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D009169:Mycobacterium tuberculosis; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011718:Pyrazinamide / Q000008:administration & dosage / Q000378:metabolism; D012293:Rifampin / Q000008:administration & dosage / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006016:Glycolates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D011718:Pyrazinamide; D019344:Lactic Acid; D007538:Isoniazid; D012293:Rifampin