Liposome-based Delivery Systems Research Articles

Development of an in vitro drug release assay that accurately predicts in vivo drug retention for liposome-based delivery systems

The therapeutic activity of numerous drugs can be dramatically improved by liposomal encapsulation. However, this requires that liposomes retain their encapsulated drugs following systemic administration. Often, in vitro drug release assays do not accurately predict the liposomal drug retention properties observed in vivo. We postulate that this discrepancy is due to the large membrane pool present in blood cells and tissues, into which drugs can distribute after in vivo administration. Herein we describe an in vitro drug release assay that more accurately predicts in vivo drug release from liposomes following systemic administration. Drug-encapsulated large unilamellar vesicles (LUVs) ∼100 nm in diameter were incubated with a 100-fold excess of multilamellar vesicles (MLVs) containing 300 mM sucrose, which served as ‘acceptors’ for drug release and transfer from ‘donor’ LUVs. Following incubation at 37 °C, the donor and acceptor populations were separated with greater than 90% efficiency by centrifugation at 1600× g for 10 min. The amount of drug in the MLV pellet reflects the degree of drug leakage from the donor liposomes. Drug release profiles using this in vitro assay were compared to those obtained using dialysis-based assays and in vivo results following systemic administration to mice. Our results indicate that this release assay is a better predictor of in vivo drug transfer than dialysis-based systems. We also demonstrate its utility in measuring exchange of lipophilic components.

Liposomes as a gene delivery system.

Gene therapy is an active field that has progressed rapidly into clinical trials in a relatively short time. The key to success for any gene therapy strategy is to design a vector able to serve as a safe and efficient gene delivery vehicle. This has encouraged the development of nonviral DNA-mediated gene transfer techniques such as liposomes. Many liposome-based DNA delivery systems have been described, including molecular components for targeting given cell surface receptors or for escaping from the lysosomal compartment. Another recent technology using cationic lipids has been evaluated and has generated substantial interest in this approach to gene transfer.