Subcutaneous nanoparticle-based antitubercular chemotherapy in an experimental model.
Poly (DL-lactide-co-glycolide) (PLG) nanoparticles encapsulating three front-line antitubercular drugs, i.e. rifampicin, isoniazid and pyrazinamide, were prepared by the multiple emulsion technique and administered subcutaneously to mice for pharmacokinetic/chemotherapeutic study. A single subcutaneous dose of drug-loaded PLG nanoparticles resulted in sustained therapeutic drug levels in the plasma for 32 days and in the lungs/spleen for 36 days. The mean residence time and absolute bioavailability were increased several-fold as compared with unencapsulated drugs. Further, drug-loaded PLG nanoparticles resulted in undetectable bacterial counts in the lungs and spleen of Mycobacterium tuberculosis-infected mice, thereby demonstrating a better chemotherapeutic efficacy, as compared with daily free drug treatment. Hence, injectable PLG nanoparticles hold promise for increasing drug bioavailability and reducing dosing frequency for better management of tuberculosis.
Pandey
Rajesh
R
Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh-160 012, India.
Khuller
G K
GK
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001682:Biological Availability; D004338:Drug Combinations; D004339:Drug Compounding; D007279:Injections, Subcutaneous; D007538:Isoniazid / Q000008:administration & dosage / Q000627:therapeutic use; D019344:Lactic Acid; D008168:Lung / Q000382:microbiology; D051379:Mice; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011718:Pyrazinamide / Q000008:administration & dosage / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D013154:Spleen / Q000382:microbiology; D014018:Tissue Distribution; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004338:Drug Combinations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D011718:Pyrazinamide; D019344:Lactic Acid; D007538:Isoniazid; D012293:Rifampin