STUDIES ON THE TISSUE DISTRIBUTION OF LIPOSOME-ASSOCIATED CLOFAZIMINE, AN ANTILEPROSY DRUG

Clofazimine, a potent antimycobacterial drug, being highly lipophilic accumulates in fat tissue and in the reticuloendothelial system causin g dose-dependent side effects. In this study, the distribution of the free drug and liposome-associated drug was compared after intravenous administration in mice. Differences in the distribution of the drug we re observed in the liver spleen, kidney and lung tissues when injected as free drug and as liposome-associated drug. Following intravenous c hallenge with the free drug, the drug accumulated quickly and high con centrations of the drug were seen in the spleen, liver, kidney and lun g even after 24 h, indicating poor clearance. However, with liposome-a ssociated drug, increased levels were seen in liver spleen and lung at 1 h with levels failing considerably at 24 h, with no accumulation in the kidney either at 1 h or 24 h after challenge. Clofazimine associa ted with neutral liposomes was preferentially targetted to spleen and lung, positively charged liposome-associated drug accumulated more in the lungs than in other tissues, while negatively charged liposome-ass ociated drug was directed to liver and spleen. The results suggest tha t inclusion of clofazimine into liposome not only targets the drug to the organs concerned but also facilitates clearance of the drug, resul ting in little accumulation. Also, renal accumulation is much lower as compared to the free drug. This suggests the potential usefulness of liposome as a carrier for clofazimine, thereby reducing the harmful si de effects due to excessive accumulation of the drug.