PDEA-PAM温敏水凝胶的制备及体外评价  

Preparation and in vitro evaluation of PDEA-PAM thermosensitive hydrogels

作　　者：赵晓曄 卜轶卓 郑云鹤 何江川 黄宇 王珂 ZHAO Xiaoye;BU Yizhuo;ZHENG Yunhe;HE Jiangchuan;HUANG Yu;WANG Ke(Department of Pharmacy,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;School of Pharmacy,Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院药学部,西安710061 [2]西安交通大学药学院,西安710061

出　　处：《西北药学杂志》2024年第3期82-89,共8页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:82204294、32171336);云南特色植物提取实验室开放研究项目(编号:YKKF2023004);浙江省自然科学基金项目(编号:LHDMY24H300002)。

摘　　要：目的制备N,N-二乙基丙烯酰胺-聚丙烯酰胺(PDEA-PAM)温敏水凝胶,将硫酸庆大霉素负载其中,并对其体外抗菌性能和体内外生物相容性进行评价。方法以N,N-二乙基丙烯酰胺(N,N-diethylacrylamide,DEA)和丙烯酰胺(acrylamide,AM)为单体,过硫酸铵(ammonium persulfate,APS)为引发剂,可降解的甲基丙烯酸酯化透明质酸(methacrylate-hyaluronic acid,HAMA)为交联剂,制备PDEA-PAM温敏水凝胶。以低临界溶液温度(lower critical solution temperature,LCST)为评价指标,用单因素变量法优化处方,并对平衡溶胀率、消溶胀率、温敏性等性能进行表征,以硫酸庆大霉素为模型药物,制备负载硫酸庆大霉素的PDEA-PAM温敏水凝胶,对其体外抗菌性能、体外体内生物相容性进行考察。结果PDEA-PAM温敏水凝胶的LCST为37℃,平衡溶胀率为58.32%,消溶胀率为21.01%,扫描电镜直观展示了PDEA-PAM温敏水凝胶分别在25、37、45℃下的网络结构变化,温敏性分析实验同样证明PDEA-PAM具有温度响应性。该水凝胶对硫酸庆大霉素的载药量为3.6%,载药水凝胶在体外对大肠杆菌和金黄色葡萄球菌均有良好的抗菌效果。同时,细胞毒性实验、溶血实验和体内器官毒性考察结果表明该水凝胶在实现体外抗菌的同时还具有良好的安全性和生物相容性。结论PDEA-PAM水凝胶实现了硫酸庆大霉素的局部使用,具有良好的温度敏感性,在体外可有效抑制细菌增殖且体外和体内生物相容性良好。Objective To prepare N,N-phenyldiethanolamine-polyacrylamide(PDEA-PAM)thermosensitive hydrogels loaded gentamicin sulphate and to evaluate the antibacterial properties in vitro and biocompatibility in vitro and in vivo.Methods PDEAPAM thermosensitive hydrogels were fabricated by using N,N-diethylacrylamide(DEA)and acrylamide(AM)as the monomers,ammonium persulfate(APS)as an initiator,and biodegradable methacrylate-hyaluronic acid(HAMA)as a cross-linker.The lower critical solution temperature(LCST)was used as the evaluation index,and the one-way variable method was used to optimize the prescription.The properties of equilibrium swelling rate,deswelling rate and temperature sensitivity were characterized.Gentamicin sulphate was used as a model drug to prepare the hydrogels,and the antimicrobial properties in vitro and biocompatibility in vitro and in vivo were investigated.Results The LCST of PDEA-PAM thermosensitive hydrogels was 37℃,the equilibrium swelling rate was 58.32%,and the dissipation rate was 21.01%.Scanning electron microscopy showed the changes in the network structure of the PDEA-PAM thermosensitive hydrogels at 25,37 and 45℃,respectively,and the thermo-sensitivity analysis test similarly demonstrated the thermal characteristics of PDEA-PAM.The loading capacity of the hydrogels for gentamicin sulphate was 3.6%,and the drug-loaded hydrogels showed good antibacterial effect against both E.coli and S.aureus in vitro.Meanwhile,the cytotoxicity test,hemolysis test and organ toxicity investigation in vivo showed the hydrogels achieved antimicrobial activity in vitro along with good safety and biocompatibility.Conclusion PDEA-PAM hydrogels implement the topical administration of gentamicin sulfate with great thermal sensitivity and biocompatibility,and effectively inhibit bacterial proliferation in vitro.

关 键 词：N N-二乙基丙烯酰胺 温敏水凝胶 硫酸庆大霉素 局部给药 

分 类 号：R97[医药卫生—药品]