Oral solid lipid nanoparticle-based antitubercular chemotherapy.
The present study was planned to evaluate the chemotherapeutic potential of oral solid lipid nanoparticles (SLNs) incorporating rifampicin, isoniazid and pyrazinamide against experimental tuberculosis. The SLNs were prepared by the "emulsion solvent diffusion" technique with an encapsulation efficiency of 51+/-5% for rifampicin, 45+/-4% for isoniazid and 41+/-4% for pyrazinamide. Following a single oral administration to mice, therapeutic drug concentrations were maintained in the plasma for 8 days and in the organs (lungs, liver and spleen) for 10 days whereas free drugs were cleared by 1-2 days. In M. tuberculosis H37Rv infected mice, no tubercle bacilli could be detected in the lungs/spleen after 5 oral doses of drug loaded SLNs administered at every 10th day whereas 46 daily doses of oral free drugs were required to obtain an equivalent therapeutic benefit. Thus, SLN based antitubercular drug therapy forms a sound basis for reducing dosing frequency and improving patient compliance for better management of tuberculosis.
Pandey
Rajesh
R
Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh 160 012, India.
Sharma
Sadhna
S
Khuller
G K
GK
D000284:Administration, Oral; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D007538:Isoniazid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008055:Lipids; D051379:Mice; D008815:Mice, Inbred Strains; D049329:Nanostructures; D011142:Polyvinyl Alcohol; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000995:Antitubercular Agents; D008055:Lipids; D011718:Pyrazinamide; D011142:Polyvinyl Alcohol; D007538:Isoniazid; D012293:Rifampin