LUNG SPECIFIC STEALTH LIPOSOMES - STABILITY, BIODISTRIBUTION AND TOXICITY OF LIPOSOMAL ANTITUBERCULAR DRUGS IN MICE

Liposomes with enhanced affinity towards lung tissue were prepared for the development of more effective chemotherapy against tuberculosis. Modification of surface of stealth liposomes by tagging O-stearylamylo pectin (O-SAP) resulted in the increased affinity of these liposomes t owards lung tissue of mice. Liposomes containing egg phosphatidylcholi ne (ePC), cholesterol (CH), dicetylphosphate (DCP), O-SAP and monosial ogangliosides )/distearylphosphatidyl-ethanolamine-poly(ethylene glyco l) 2000 (DSPE-PEG 2000) were found to be most stable in serum. Tissue distribution of these liposomes showed more accumulation in lungs than in reticuloendothelial systems (RES) of normal and tuberculous mice. Pre administration of PC and CH (2:1.5) liposomes before the injection of lung specific stealth liposomes further enhanced their uptake in l ungs. In vivo stability of these liposomes demonstrated the slow and c ontrolled release of their encapsulated contents. Isoniazid and rifamp icin encapsulated in liposomes were less toxic to peritoneal macrophag es as compared to free drugs. Further, encapsulated drugs also demonst rated reduced in vivo toxicity in comparison to free drug(s). These fi ndings suggest liposomes to be better drug delivery vehicles for exper imental tuberculosis.