Studies On Interaction Between Biodegradable Uncharged Polymers And Liposomes

Liposomes are microparticulate lipoidal vesicles which are extensively investigated as biomimetic membranes and carriers for drug delivery and gene transfection because of their unique structure.In the research background section, we review the recent advances in the liposomes for biomedical applications, including drug controlled release and gene delivery. The interactions between polymers and liposome vesicles, and interaction mechanisms are also discussed.The research carried out can be divided into two parts. The first part investigated the effects of a hydrophilic polymer poly-a,P-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) and an amphiphilic polymer PHEA-g-poly(2,2-dimethyltrimethylene carbonate) (PHEA-g-PDTC) on phosphatidylcholine liposome vesicles. The hydrophilic polymer PHEA has a strong destabilizing effect on the liposomes and induces immediate liposome membrane leakage and aggregation. While the destabilizing effect of the amphiphilic polymer PHEA-g-PDTC is weaker. The in situ observation of shape transformations of a vesicle indicates that addition of PHEA increases amplitudes of the fluctuations of the vesicle membrane, finally leading to burst of the vesicle. The existence of hydrogen bonding between the polymers and the liposome membranes is the main reason for inducing destabilization. The molecular structure, such as the stiffness of the polymer backbone and the spacer connecting the hydroxyl group with the backbone, of the polymers greatly affect the interaction between the polymers and the vesicles.In the second part of our research, we prepared a series of biodegradable polymers/oligomers based on E-caprolactone (CL) end-functionalized by cholesteryl moiety. The functionalized polymers/oligomers, Chol-(CL)n, were synthesized through ring-opening polymerization initiated by cholesterol with a hydroxyl group. Thechemical structure of end-functionalized polymers/oligomers was confirmed by FTIR and 1H NMR. The molecular weight of the functionalized polymer/oligomer can be accurately controlled by adjusting the feed ratio of the initiator cholesterol to the monomer CL. Incorporation of cholesteryl moiety to the polymer chain results in liquid crystallinity of the resulting polymer/oligomer. The temperature range in which liquid crystallinity exhibits is greatly dependent on the molecular weight of the functionalized polymer/oligomer. The Toom-temperature liquid crystallinity can be obtained for the functionalized oligomer. These functional polymers/oligomers are promising in preparing self-assembling drug delivery systems, and liposomal vesicles for the fundamental study of liposomes.