Targeted Delivery of Drugs and DNA with Liposomes

Abstract

This presentation is divided into three parts: long-circulating liposomes, immunoliposomes and gene transfer with liposomes. The mechanism of action for the poly(ethylene glycol)-phospholipid conjugates to prolong the circulation time of liposomes can be understood on the basis of steric barrier activity imposed by the flexible PEG chains on the liposome surface. The action of ganglioside GM₁, on the other hand, probably involves specific interactions with serum protein(s). Immunoliposomes can efficiently bind with the target only if the target is readily accessible and the liposomes stay in the circulation for a relatively long period of time. Coating the liposome surface with PEG chains or GM₁ enhances the target binding of immunoliposomes, except when PEG of greater than 5000 dalton is used. In this case, immunoliposome binding to the target is sterically hindered by the long PEG chains. To overcome the problem, antibody molecule is conjugated to the distal end of the PEG chain. This approach works well except that the liver uptake of immunoliposomes is somewhat enhanced. For the delivery of DNA into cells, a novel cationic amphiphile (DC-chol) is synthesized and is now used in clinical trials of gene therapy for melanoma. Current effort is concentrated on the means to enhance the level and duration of transgene expression.