Materials Engineering of Lipid Bilayers for Drug Carrier Performance

The liquid-phase lipid bilayer is a unique engineering material. Biologically, it holds a central position in cellular life, providing the structural basis for the membrane that surrounds every cell on the planet. From a materials perspective, it is essentially a 4-nm-thick, water-insoluble sheet of 2-poise oil. Artificial membranes were “discovered” 35 years ago. It was soon recognized that liposomes could have a range of potential uses, and investigators sought to exploit the obvious capsular and biocompatibility properties of the membrane in applications such as liposome drug delivery. Since 1966, some 18,000 papers on liposomes have appeared in the literature (listed on Medline, and see References 4–7 for reviews), and 260 patents have been issued describing the use of liposomes in the pharmaceutical industry. These patented applications have included the delivery of cancer drugs, intracellular drug delivery, inhalation, topical drugs, gene therapy, proteins, peptides, amino acids, vaccines, targeted liposomes, lipophilic drugs, and liposome production, separation, and analysis. A huge database therefore exists with which to establish boundary conditions for predicting under which circumstances the encapsulation of drugs in liposomes or other carriers may be expected to result in improved therapy. Despite this enormous effort, only a few formulations, principally for amphotericin (an antifungal drug) and anthra-cyclins (anticancer drugs), have been approved and marketed, heralding the promise and potential that these versatile lipid-bilayer materials present. The reasons for this limited success are many, not the least of which is that the cost of developing a new pharmaceutical product can be several hundred million dollars.