Applications of lipid vesicles: Drug delivery systems and templates for nanometer and micron sized structures

The pH-dependent conformational transition of poly(2-ethylacrylic acid) [PEAA] was investigated by fluorescence spectroscopy using pyrene as a probe. We demonstrate that solvent fractionation is effective in reducing the polydispersity of a PEAA sample obtained from bulk free-radical polymerization, and in providing PEAA fractions of various molecular weights. The breadth of the conformational transition was reduced by using samples of lower polydispersity. Furthermore, the location of the conformational transition on the pH axis was shown to be dependent upon the molecular weight of the sample. The interaction of PEAA with phosphatidylcholine vesicles was studied. PEAA was shown to induce fusion of phosphatidylcholine bilayer membranes under mildly acidic conditions. The pH-dependent destabilization and fusion of extruded large unilamellar vesicles (LUVs) by PEAA was characterized by optical density measurements, transmission electron microscopy, and lipid mixing and contents release assays. Reduction of either the chain length or the polymer concentration caused the fusion and contents release events to shift to lower pH values. Release of entrapped calcein was observed at pH values ca. 1 unit higher than those found to cause membrane fusion. Decreased levels of fusion were observed when the concentration of PEAA was lower than that of the lipid; however, quantitative release of encapsulated calcein could be effected at very low polymer concentrations (∼3% w/w PEAA/lipid). Giant unilamellar vesicles were used as templates for producing flexible polymeric wires. Tubes up to several microns in diameter formed spontaneously upon dehydration of the vesicles, or were formed mechanically by shearing the vesicle to create the appropriate membrane instability. The resulting tubes were stabilized by photopolymerization of poly(ethylene glycol) dimethacrylate [PEGDMA], the lumenally confined macromonomer. A detailed study of the mechanical properties of crosslinked PEGDMA filaments was performed. Four different molecular weight PEGDMAs were synthesized from the corresponding dihydroxy terminated poly(ethylene glycol) and methacroyl chloride. Mechanical properties of bulk hydrogels were measured via tensile testing with an Instron, and these values are compared to those obtained on micron sized filaments connecting two spheres (hydrogel dumbbell) by stretching the dumbbells in a flow field. Furthermore, techniques were developed for drawing a nanotube (or an array of tubes) between gold contacts on a surface. We have also demonstrated the use of this templating approach to produce pH-responsive hydrogels composed of poly(ethylene glycol) dimethacrylate and methacrylic acid