Intracellular Delivery of DNA and Proteins Using Vinyl Ether-Based Drug Delivery Vehicles

Liposomal carriers are an attractive approach for drug delivery due to their biocompatibility and their large loading capacities for either hydrophilic or hydrophobic drugs. Liposomal drug formulations have been slow to penetrate the marketplace because of limited stability and site-specific delivery, and inefficient drug release at the site of action. Our group has developed an efficient drug delivery strategy using acid- or photooxidatively labile plasmenyl-type liposomes. Cleavage of these lipids leads to morphology changes of the liposomal membrane. These phase transitions have been used to promote intracellular drug delivery. For example, cyto-toxic drugs (Ara-C and AlPcS44-) were successfully delivered via folate-targeted DPPlsC liposomes. The cytotoxicity of these formulations was significantly higher than free drug, non-targeted liposomal drug, or targeted acid-insensitive liposomal drug controls. These results clearly show the synergistic effect of combined targeting and triggering.