Pharmacokinetics of long-circulating liposomes

Association of drugs with carriers such as liposomes has marked effects on both the pharmacokinetic profiles of the carrier and of the carrier-associated drug. In general, association of drugs with liposomes delays drug absorption, alters and restricts drug biodistribution, decreases the volume of distribution, delays clearance and retards drug metabolism. Surface modification of liposomes by the inclusion of hydrophilic components (e.g., carbohydrates, glycolipids or polymers) to form long-circulating liposomes causes changes in the pharmacokinetic pattern seen for unmodified (classical) liposomes. While classical liposomes have non-linear, saturable kinetics, long-circulating liposomes possess dose-independent, non-saturable, log-linear kinetics. The log-linear kinetics for long-circulating liposomes results from a significant decrease in the first phase of clearance into a high affinity, low capacity system, probably the cells of the mononuclear phagocyte system. An understanding of the pharmacokinetics of liposome-associated drugs is critical to the development of rationale strategies for therapeutic applications of long-circulating liposomes.