Synthesis of dextran-based hydrogels, their characterization, structural study, and drug control release property.

摘要

The objective of this study was to design new classes of dextran-based biodegradable hydrogels by a variety of chemical methods. The swelling property, morphology of three-dimensional network structure, and the controlled release profiles of several model compounds from these new hydrogels were examined.; Dextran was chemically modified to incorporate different types of unsaturated moieties as hydrogel precursors. Long-wavelength UV photocrosslinking was employed to convert the precursors into hydrogels. Three types of photocrosslinkable dextran derivatives (acrylated dextran, dextran-maleic acid, dextran-methacrylate) were developed and their syntheses were examined as a function of reaction parameters. The chemical structure of the hydrogel precursors, degree of substitution (DS), and photocrosslinked hydrogels were studied by FT-IR, 1H-NMR, 13C-NMR, and HMQC.; Acrylated dextran was prepared by first bromoacetylating dextran by bromoacetyl bromide and subsequently reacting bromoacetyl dextran with sodium acrylate for incorporating vinyl group. Various degrees of bromoacetyl substitution (0.19, 0.49. 1.42, and 2.99) were obtained by different reaction conditions.; Dextran-maleic acid was synthesized by the reaction of dextran with maleic anhydride in the presence of triethylamine a catalyst. The new hydrogel precursor had an excellent solubility in various common organic solvents. Dextran-maleic acid hydrogel showed a very high swelling ratio in water, and the magnitude of swelling depended on the pH of the medium and DS.; Dextran-methacrylate was synthesized by reacting dextran with methacrylic anhydride in the presence of triethylamine catalyst. Dextran-methacrylate showed an enhanced solubility in common organic solvents. Dextran-methacrylate hydrogel showed swelling ratio ranging from 67% to 227%. SEM observation of a cryofixed swollen hydrogel showed a three-dimensional porous structure, but the unswollen hydrogel did not exhibit any visible pores. Mercury intrusion porosimetry provided quantitative characterization of pore structure.; In vitro drug release behaviors of Doxorubicin RTM, Alizarin Red S, FITC-dextran, and L-lysine from the dextran-methacrylate hydrogels, were studied. Delayed release of drugs was observed with these hydrogels having a higher DS. As molecular weight of drugs increased, the cumulative amount of drug release decreased. Release of these three model compounds followed a simple Fickian diffusion at an early stage of release and the threshold size of drugs for release was 10,000.