ABSTRACT
The use of a relatively inexpensive and easily prepared lipid, PEG-PE, given its abilities to avoid MPS uptake, has transformed the pharmaceutical development of liposomes and restored much of the original promise of liposomes, as well as opened up entirely new applications ranging from drug delivery systems with dramatically changed pharmacokinetics and biodistribution to providing a more realistic model for the study of biological membranes, red blood cells, cell-cell, protein-cell, and receptor interactions. The current hypothesis is that the long circulation results from reduced adherence of plasma "opsonin" components, based on extension of the known property of polymers to stabilize colloids through what is often called steric stabilization. 12·18·19 Many varied physical measurements appear to substantiate this proposed mechanism.20·21 Although this aspect needs further investigation and confirmation,22 such liposomes have become known as sterically stabilized liposomes or SSL, including extensions of this terminology, e.g., SSIL for sterically stabilized immunoliposomes. 19·23
Fortunately, the lack of a complete understanding of the mechanism of action has not impeded the evaluation of these novelliposomes for their usefulness in a number of different therapeutic applications. SSL containing anticancer drugs have demonstrated improved efficacy in preclinical animal models24 and these findings have been reflected in encouraging initial results from ongoing clinical studies.25 Other efficacy studies have evaluated the use of SSL in prolonged delivery of a bioactive peptide hormone26 and antibioticsY
Lipid transfer occurs by two separate processes: either by associated transfer proteins or, in some instances, with no other apparent interactions, i.e., via molecular solubility in the aqueous phase or upon events during particle-particle collisions. It was recognized early on that lipid exchange, including the exchange of cholesterol, is apparently not dependent on enzymatic activity.30•31 A number of reports of liposome fusion measured by the transfer of lipid markers were later shown to be the result of lipid exchange,32•33 demonstrating that it can occur in the absence of lipid transfer proteins. The exact mechanisms of lipid exchange are unresolved.
