Bruce Bondurant

Photoinitiated destabilization of sterically stabilized liposomes

A considerable effort has been devoted to the development of liposomes for the transport and buffering of drugs in the body. Several research groups have reported the increased localization of sterically stabilized liposomes (PEG-liposomes) at tumor sites. If PEG-liposomes are to be effective carriers of therapeutic agents, their drug permeability must be sufficiently low that little passive release occurs during the circulation time of the PEG-liposomes. However, once PEG-liposomes reach tumor sites, it may be desirable to accelerate the release of the encapsulated drug. The use of light to stimulate the release of encapsulated compounds from liposomes is attractive, because it is possible to control the spatial and temporal delivery of the radiation. PEG-liposomes composed in part of the photosensitive lipid, bis-SorbPC, can be prepared in a manner that effectively encapsulates water soluble compounds, yet releases them upon exposure to ultraviolet light in the presence of oxygen. The observed increase in liposome permeability is about 200-fold at high photoconversion of the monomeric bis-SorbPC. The increase in permeability is dependent on the extent of photolysis, but independent of both the charge on the PEG-lipid and the mole fraction of PEG-lipid included in the liposome. Therefore the photoinitiated destabilization of these PEG-liposomes is not a consequence of micellization of the PEG-lipid, but probably due to the formation of defects in the bilayer during crosslinking of the bis-SorbPC. The photoinduced increase in liposome permeability is great enough to make it possible to release therapeutic agents from PEG-liposomes at specific sites in a manner of tens of minutes to hours.

Polymerization of supramolecular assemblies: Comparison of lamellar and inverted hexagonal phases

Abstract Since the first reports of the polymerization of hydrated bilayers in the early 1980s, a wide variety of polymerizable groups and lipids has been successfully employed. Among the various strategies explored for the polymerization of lamellar phases, a particularly useful method relies on the design of suitable polymerizable amphiphiles, which upon hydration form assemblies that can then be polymerized with retention of structure. We have recently extended this strategy to successfully polymerize the inverted hexagonal (H II ) phase. This report is the first comparison of radical chain polymerizations in lamellar and H II phases. The number average degree of polymerization of polymers obtained in both lamellar and H II phases depended strongly on the initiation chemistry, but were insensitive to the lipid phases. The immediate benefit of these studies is the knowledge that polymer size can be varied extensively in both phases in order to obtain different materials properties.

Nanostructured Materials Integrated in Microfabricated Optical Devices

This project combined nanocomposite materials with microfabricated optical device structures for the development of microsensor arrays. For the nanocomposite materials we have designed, developed, and characterized self-assembling, organic/inorganic hybrid optical sensor materials that offer highly selective, sensitive, and reversible sensing capability with unique hierarchical nanoarchitecture. Lipid bilayers and micellar polydiacetylene provided selective optical response towards metal ions (Pb(II), Hg(II)), a lectin protein (Concanavalin A), temperature, and organic solvent vapor. These materials formed as composites in silica sol-gels to impart physical protection of the self-assembled structures, provide a means for thin film surface coatings, and allow facile transport of analytes. The microoptical devices were designed and prepared with two- and four-level diffraction gratings coupled with conformal gold coatings on fused silica. The structure created a number of light reflections that illuminated multiple spots along the silica surface. These points of illumination would act as the excitation light for the fluorescence response of the sensor materials. Finally, we demonstrate an integrated device using the two-level diffraction grating coupled with the polydiacetylene/silica material.