Chapter 1: Lipid Microvesicles: On the Four Decades of Liposome Research

Abstract

In the past four decades, liposome research in areas ranging from biophysics and bioreactors to medicine has been growing. This chapter focuses on the formulation development of liposomes as pharmaceutical carriers in the past 10-15 years. One of the major breakthroughs in the evolution of liposomal formulation is the development of sterically stabilized liposomes (SSL) by coating liposomes with polymer. This can sterically hinder a variety of interactions at the bilayer surface, so that the liposomes can escape the rapid uptake by macrophage cells of reticuloendothelial system, and circulate in the blood stream for a long time and passively target into sites of tumors, infection, and inflammation characterized by the presence of a leaky vasculature. With the successful development of SSL, it has been possible to investigate strategies of site-specific targeting and triggered drug release. To obtain elevated abnormal-to-normal tissue biodistribution ratio, active site-targeting liposomes were developed by attaching antibodies or ligands to the exterior surface of the polymer coating or directly to the liposome surface by chemical conjugation. In addition, several promising strategies of active triggered intracellular delivery of liposomal drugs have emerged, including external light and thermal triggering and endogenous pH and enzyme triggering. By adjusting the lipid composition and by the combination of all these strategies on a single liposome pharmaceutical carrier, a promising method for optimizing the therapeutic effect of liposomal drugs is emerging. © 2006 Elsevier Inc. All rights reserved.