Synthesis, characterization, and property study of hydrophilic-hydrophobic biodegradable hydrogels as a controlled drug delivery system.

摘要

We synthesized a new class of biodegradable hydrogel networks consisting of hydrophobic poly (D,L) lactic acid (PDLLA) and hydrophilic dextran segments using UV photocrosslinking. By adjusting the composition ratio and molecular weight (MW) of these two polymer constituents, a wide range of hydrophilicity to hydrophobicity, swelling, degradation, thermal and mechanical properties could be controlled.; We first reported the synthesis of the biodegradable hydrogel based on dextran and PDLLA. Unsaturated vinyl groups were introduced onto the PDLLA chain ends and dextran polymer backbones to prepare hydrogel precursors for subsequent UV crosslinking to generate a hydrogel having 3D network structure. The effects of reaction conditions on the synthesis of PDLLA diacrylate macromer (PDLLAM), dextran derivative of acryloyl chloride (dex-AC), and dextran derivative of allyl isocyanate (dex-AI) were studied. A series of hydrogels with different composition ratios were then prepared by UV photocrosslinking of the unsaturated groups. These newly synthesized polymers and hydrogels were characterized by standard polymer characterization methods like NMR, FTIR, and GPC.; The swelling study showed that a wide range swelling property was obtained by changing dextran derivatives to PDLLAM composition ratio, type and degree of unsaturated groups incorporated into dextran, UV photocrosslinking time, solvent extraction, and MW of hydrogel precursors. We also found that the hydrolytic degradation, mechanical strength, and thermal property changes of the hydrogels depended upon the composition ratio and MW of the PDLLA and dextran.; When these biodegradable hydrogels were used as drug carriers, the release of drugs could be controlled by the chemical structure of drugs and polymer components, drug size, porosity, and permeability of the hydrogel, the rate of degradation of hydrogels, and diffusion of drugs. According to the release kinetics study of three model drugs (indomethacin, insulin and bovine albumin), as the PDLLAM composition increased, the diffusion coefficient of a small but moderately hydrophobic drug, indomethacin, decreased due to less swelling-induced pores in the hydrogels and higher hydrophobic interaction between indomethacin and PDLLAM component. For higher MW drugs, such as insulin and albumin, their sustained rate and extent of release increased as the PDLLAM composition increased due to the faster formation of a loose and more open 3D network structure as a result of increased hydrolytic degradation of the hydrogel.