Chemotherapy of Mycobacterium tuberculosis infections in mice with a combination of isoniazid and rifampicin entrapped in Poly (DL-lactide-co-glycolide) microparticles.
Strategies to improve patient compliance in tuberculosis chemotherapy include the use of sustained release drug delivery systems. In this study, Poly (DL-lactide-co-glycolide) (PLG) microparticles containing a combination of isoniazid and rifampicin were developed as sustained release carrier systems. A single dose of PLG microparticles exhibited a sustained release of isoniazid and rifampicin in vivo up to 7 and 6 weeks, respectively. Free drugs (in combination) injected in the same doses were detectable in vivo up to 24 h only. One dose of PLG microparticles cleared bacteria more effectively from lungs and liver in an experimental murine model of tuberculosis after low-dose PLG combination drug therapy and in liver after high-dose PLG combination drug therapy as compared with a daily administration of the free drugs. These results suggest that PLG microparticles offer an improvement for tuberculosis chemotherapy over the conventional treatment.
Dutt
M
M
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India.
Khuller
G K
GK
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D002214:Capsules; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D005260:Female; D007538:Isoniazid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000378:metabolism
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D002214:Capsules; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007538:Isoniazid; D012293:Rifampin