【摘要】 提高药物控释智能水凝胶的稳定性,降低降解速度,对其应用于长期释药具有重要意义。利用甲基丙烯酸酐(MA)对透明质酸(HA)进行化学改性,得到甲基丙烯酰化透明质酸(HAMA),以HAMA和N-异丙基丙烯酰胺(NIPAM)为前驱体,以过硫酸铵(APS)为引发剂,利用自由基聚合反应制备了系列HAMA/NIPAM-x复合水凝胶,并对水凝胶的凝胶时间、溶胶-凝胶转化、微观形貌、溶胀、降解、流变学性能以及体外载牛血清白蛋白(BSA)模型药物的释放行为进行了研究。结果表明,系列水凝胶具有连续的三维网络结构,在不同温度下(25,30,32,37℃)均能快速达到溶胀平衡,平衡溶胀率15～23,水凝胶表现出良好的温度敏感性,随着温度升高,其溶胀率下降;在PBS溶液(p H值7.4)中30 d降解百分数5%～26%,稳定性好;具有良好的力学强度和剪切变稀特性;药物(BSA)负载率较高,达到76%,载药水凝胶在PBS溶液(p H值7.4)中10 d累积释放率66%～99%,其中HAMA/NIPAM-5在30℃时累积释放率最高,接近99%。系列水凝胶具有较好的稳定性、药物负载能力和药物控释能力,在中长期药物释放领域具有潜在的应用价值。更多还原

【Abstract】 It is of great significance to improve the stability and reduce the degradation rate of intelligent hydrogels for long-term drug controlled release. In this paper,HA was chemically modified by methacrylate anhydride( MA) to obtain methacryloylated hyaluronic acid( HAMA). By using HAMA and N-isopropylacrylamide( NIPAM) as precursors,a series of HAMA/NIPAM-x composite hydrogels were prepared via free radical polymerization with ammonium persulfate( APS) as initiator. The gel time,sol-gel transformation,microstructure,swelling,degradation,rheological properties and the in vitro release behavior of bovine serum albumin( BSA) were investigated. The results show that the series of hydrogels have a continuous three-dimensional network structure,and can reach swelling equilibrium rapidly at different temperatures( 25,30,32,37 ℃) ． The swelling equilibrium ratio ranges from 15 to 23,and the hydrogels show good temperature sensitivity. With the increase of temperature,the swelling ratio decreases. In PBS solution( pH = 7. 4),the degradation percentage ranged from 5% to 26% after immersing30 days,indicating that the series of hydrogels have good stability. The series of hydrogels have good mechanical strength and obvious shear thinning characteristics. The loading ratio of BSA was about 76%,the cumulative release percentage of BSA-loaded hydrogels ranged from 66% to 99% in PBS solution( p H =7. 4) for 10 days,and the cumulative release percentage of BSA-loaded HAMA/NIPAM-5 was the highest at 30 ℃,approaching 99%. The series of hydrogels could be potentially used in the fields of short medium and long-term drug release because of their good stability,drug loading capacity and drug controlled release capacity.更多还原