| The newly emerged biotechnology of liposome-based drug delivery has drawn great interest in research and pharmaceuticals.; My research on developing controlled release drug delivery systems started with the synthesis of a highly reliable anchor for water-soluble polymers, which will serve as an anchor with a high affinity towards lipid bilayers and can be monitored by fluorescence. A new family of hydrophobic building block, namely cholesterol and fluorescence groups, was prepared and characterization. The conformation study suggests that intramolecular hydrogen bonds form via the amide proton of these compounds in methanol-d3 and DMSO-d6. Furthermore, an efficient synthetic route was developed to synthesize the corresponding pyrenylbutyl cholesterol lysine derivative.; These functional hydrophobic building blocks were successfully attached to water-soluble polymers such as poly(N-isopropylacrylamide). Solution properties of the modified polymers were investigated by fluorescence, time-resolved fluorescence, and dynamic light scattering. The cholesterol bearing PNIPAM exhibited the lower critical solution temperature (LCST), which was close to that of the precursor polymer. The polymers formed micellar aggregates in water via inter or/and intrapolymeric associations, which depended on the polymer architecture and solution temperature.; Interaction of phospholipid and nonphospholipid liposomes with these thermoresponsive polymers was followed in order to develop controlled release systems based on cholesterol-bearing poly(N-isopropylacrylamide) coated liposomes. The strong interaction between the polymer and liposomes was found via fluorescence and gel-filtration chromatography measurement. As expected, the cholesterol-bearing polymers remained on the liposome surfaces as increasing temperature up to 60°C. In contrast, above the LCST of PNIPAM, octadecyl group modified PNIPAM escaped from liposome surfaces and left liposome unprotected. Interesting results were also found in the study of temperature controlled release and target fusion of these polymers coated liposomes.; In addition, controlled release systems based on hybrid polymeric nanoparticles formed by self-assembled cholesterol-bearing pullulan and poly(N-isopropylacrylamide) (PNIPAM) were studied. The hybrid nanoparticles further proved that cholesterol was a reliable anchor, which remained in hydrophobic microdomains of the hybrid nanoparticles in the studied temperature range from 20 to 45°C. (Abstract shortened by UMI.)... |
