Hybrid Vesicle Composed Of Cholesterol Modified Dextran And PLA: Formation Mechanism And Drug Release

Cholesterol-3-hemisuccinyl chloride was synthesized by cholesterol and succinic anhydride in anhydrous pyridine, which was characterized by infrared spectroscopy, cholesterol hydrophobically modified dextran (Dex-CH) was obtained by esterification of dextran cholesterol 3-hemisuccinyl chloride using anhydrous dimethyl sulfoxide (DMSO) as solution and terethylamine as catalyst, substituted degree can be controlled by the ratio between dextran and cholesterol 3-hemisuccinate, the actual substituted degree was analysized by 1H-NMR spectra.Poly(acrylic acid) and Dex-CH were dissolved in DMSO in certain proportion, then dialysis against deionized water, PLA/Dex-CH vesicle was prepared. From the experiment, it indicated that the vesicle formation was highly dependent on the proportion of PLA and Dex-CH, the molecular weight of PLA was 5×104 g/mol and dextran was 4×104 g/mol, substituted degree was 8%, when the ratio of PLA and Dex-CH was in the range of 1:7 and 2, vesicle structure was formed, which can be observed by Transmission Electronic Microscopy (TEM). Gadolinium Chloride (GaCl3), contrast medium, could increase the vesicle contrasts, in the condition of higher magnification time, the vesicle layer was sandwich structure; the fluorescence spectra technology can indicate the existence of hydrophobic microdomains. In 1HNMR spectra, the signal of PLA and cholesterol molecules were significantly broadening and loss in resolution demonstrated that the vesicle formation was controlled by hydrophobic-complexation, through that interaction, PLA was just like a long chain molecule grafted on to dextran.In different proportion of PLA and Dex-CH, change the molecular weight of PLA, vesicle could formed in the middle proportion, and there were no relationship to PLA molecular weight; the substituted degree were 4%,8%,17%,26%, respectively, and change the substituted degree, vesicle structure could be formed, vesicle structure could not be formed in higher or lower substituted degree; dextran with different molecular weight (5×104 g/mol, 105 g/mol, 3×105 g/mol, 5×105 g/mol), vesicle structure could be formed; vesicle stability could be investigated by zeta potential and turbidity.The hydrophilic drug cefradine could be loaded into vesicles, drug loading rate and drug release were investigated. The actual drug loading rate was 31.73% and the encapsulation efficiency was 32.39%; in the condition of different substituted degree, that is 4%, 8% and 17%, vesicles with lower substituted degree had faster drug releasing rate, which lasted 14,vesicles with higher substituted degree had slower release rate, about 25h.