Materials Engineering of Lipid Bilayers for Drug Carrier Performance
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promise and potential that these versatile lipid-bilayer materials present. The r e a s o n s for t h i s l i m i t e d success are many, not the least of which is that the cost of developing a new pharmaceutical product can be several hundred million dollars. From a materials-engineering standpoint, much of this development has been somewhat empirical, and liposome formulations have not necessarily been guided by materials data for lipid bilayers. Various micropipet methods have been developed since 1980 to specifically study the m e c h a n o c h e m i c a l features of lipid-bilayer vesicles. The information gained from such studies not only characterizes the membrane and its intermembrane interactions from a fundamental materials-science perspective, it also p r o v i d e s essential m a t e r i a l s property data that are required for the successful design a n d deployment of lipid-vesicle capsules in applications such as drug delivery. Here, the strength and compliance of the membrane, its interfacial interactions, its transition properties, and its exchange with drugs and other molecules are of particular interest. The first materials-property data on giant lipid-vesicle bilayers were obtained in 1980 by Kwok and Evans 13 using a micropipet manipulation technique. The glass micropipet, with precise control over applied hydrostatic pressures, provides a unique way of applying welldefined stresses to a single giant lipid vesicle while simultaneously acting as a sensitive transducer of vesicle membrane area, shape, and volume change. Using a
suction pipet, a single lipid vesicle can be aspirated and manipulated, and several mechanochemical experiments can be performed (see References 14 and 15 and references therein, especially papers by Evans and by Waugh). This technique has been used to characterize the following properties on single giant lipid vesicles: membrane-area expansion; tensile failure and bending for liquid and solid membranes; shear yield strength and shear viscosity for solid-phase m e m b r a n e s ; t h e r m a l bilayer t r a n s i t i o n s ; adsorption, uptake, and desorption of various membrane-binding and membrane-soluble components; membrane water-permeability coefficient; and transmembrane pore formation due to the action of an electric field or uptake of macromolecular structures. The ability to manipulate pairs of vesicles has also allowed the measurement of the intermembrane adhesion energy that results from the cumulation of several attractive (including van der Waals and polymer) and repulsive (hydration, electrostatic, undulation, and polymer steric) colloidal potentials. The fusion between two vesicles has also been observed as a result of electroporation and defect formation due to the inclusion of nonbilayer phospholipids; in a recent, more sophisticated development of the micropipet technique, adhesion mediated by specific receptor-ligand bonds has been quantified down to the level of single molecular bonds. 16 Over the last 30 years, lipid-based drug carrier systems hav
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