ABSTRACT
It is now recognized that drug delivery systems can improve the pharmacological properties of many drugs, resulting in increased circulation lifetimes and enhanced efficacy (1). This is often due to altered pharmacokinetic and biodistribution properties of the drugs, which result from their encapsulation within a specific drug carrier system. In recent years, a variety of lipid-or polymer-based nanoparticles have been developed and characterized including liposomes (2), micelles (3), dendritic unimolecular micelles (4), and polymeric nanospheres (3,5), to name a few. Of these many systems, perhaps the best characterized, and certainly one of the first to be developed, were the liposomes, small artificial lipid bilayers with diameters in the nanometer-tomicrometer size range. Although first discovered over 35 years ago, when it was observed that lipids dispersed in water spontaneously formed large multilamellar vesicles (6), a significant amount of technological development was required before their full potential as drug delivery systems could be realized. In addition to a thorough knowledge of the physical properties
of lipids in membranes (such as the effect of lipid composition on membrane permeability), this included techniques for the rapid generation of unilamellar vesicles possessing an optimal size and narrow size distribution, and for the encapsulation of drugs and macromolecules within them. The first requirement was met by the development of extrusion technology, and the latter by the use of pH gradients as a driving force for the accumulation of weakly basic drugs in the interior of acidic vesicles.
