氧化透明质酸/聚丙烯酰肼水凝胶的制备及性能

Preparation and Properties of Oxidized Hyaluronic Acid/Polyacryloyl Hydrazide Hydrogels

以丙烯酸甲酯（MA）为原料合成了聚丙烯酸甲酯（PMA）,PMA与水合肼反应制备了聚丙烯酰肼（PAH）,用高碘酸钠对透明质酸（HA）进行部分开环氧化,制备了氧化透明质酸（oxi-HA）,PAH与oxi-HA通过席夫碱反应制备了系列oxi-HA/PAH水凝胶。利用1HNMR、FTIR对PMA、PAH、oxi-HA进行了结构表征,用多角度激光光散射系统（MALLS）测定了PMA的相对分子质量,采用试管倒置法、SEM、称重法、旋转流变仪、Bradford法对水凝胶的凝胶时间、微观形貌、溶胀率、降解行为、流变学性能,及体外药物控释性能进行了考察。结果表明,水凝胶的凝胶时间介于8~205 s,具有连续的三维网络结构及较好的粘弹性和力学强度;在37℃的磷酸盐缓冲溶液（PBS,pH=7.4）中,水凝胶7 h溶胀率介于12~22,oxi-HA60/PAH30水凝胶20 d降解率为66%左右,载药oxiHA60/PAH30水凝胶中模型药物牛血清蛋白（BSA）10 d累积释放率约86%。

Polymethyl acrylate（PMA） was synthesized using methyl acrylate（MA） as raw material,followed by aminolysis of PMA using hydrazine hydrate,to prepare polyacryloyl hydrazide（PAH）.Hyaluronic acid（HA） was partially oxidized by sodium periodate to creat oxidized hyaluronic acid（oxi-HA）. A series of oxidized hyaluronic acid/polyacryloyl hydrazide（oxi-HA/PAH） hydrogels were prepared via Schiff base reaction between oxi-HA and PAH. The structures of PMA,PAH,and oxi-HA were characterized utilizing1 HNMR and FTIR. The molecular weight of PMA was determined using multi-angle laser light scattering system（MALLS）. The gelling time,microtopography,swelling ratio,degradation behavior,rheological properties and in vitro drug release performance of hydrogels were investigated by the vial inversion method,SEM,weighing method,rotational rheometer and Bradford method,respectively. The results showed that the gelling time of oxi-HA/PAH hydrogels ranged from 8 s to 205 s,and the hydrogels with continuous three-dimensional network structure exhibited suitable viscoelasticity and mechanical strength. In phosphate buffer solution（PBS,pH 7. 4） at 37 ℃,the swelling ratio of hydrogels ranged from 12 to 22 after 7 hours. The degradation percentage of oxi-HA60/PAH30 hydrogel was about 66% after 20 days,and the cumulative release percentage of bovine serum albumin（BSA） as model protein drug from drug-loaded oxi-HA60/PAH30 hydrogel was about 86%after 10 days.