title: Subcutaneous nanoparticle-based antitubercular chemotherapy in an experimental model.
abstract: 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.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh-160 012, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Pandey
authors.forename: G K
authors.initials: GK
authors.lastname: Khuller
mesh_terms: 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
chemical_list: 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