PVP-semi-IPN-PCL/PLA水凝胶制备及负载卡马西平药物共晶体外释放  

Preparation and in vitro Release of Carbamazepine Cocrystal of PVP-semi-IPN-PCL/PLA Hydrogels

作　　者：朱杰 李琪 王子萌 陈旸 高玲焕 梁子源 乔宁 ZHU Jie;LI Qi;WANG Zi-meng;CHEN Yang;GAO Ling-huan;LIANG Zi-yuan;QIAO Ning(College of Materials Science and Engineering,North China University of Science and Technology,Tangshan 063210,China;School of Pharmacy,North China University of Science and Technology,Tangshan 063210,China;School of Basic Medical Sciences North China University of Science and Technology,Tangshan 063210,China)

机构地区：[1]华北理工大学材料科学与工程学院,唐山063210 [2]华北理工大学药学院,唐山063210 [3]华北理工大学基础医学院,唐山063210

出　　处：《高分子通报》2022年第8期47-53,共7页Polymer Bulletin

基　　金：河北省教育厅科学技术研究项目(JYG2020002);华北理工大学大学生创新创业训练计划(R2020082);华北理工大学教育教学改革研究与实践项目(L2048);唐山市功能高分子材料基础创新团队(21130201D)。

摘　　要：通过N-乙烯基吡咯烷酮(N-vinyl pyrrolidone,NVP)在聚己内酯(polycaprolactone,PCL)、聚乳酸(poly(lactic acid),PLA)乙酸乙酯溶液中自由基聚合,制得聚乙烯吡咯烷酮(Polyvinylpyrrolidone,PVP)/聚己内酯、聚乳酸半互穿网络(semi-interpenetrating network,semi-IPN)水凝胶(PVP-semi-IPN-PCL/PLA)。实验制得疏水/亲水比例分别为1∶9、3∶7、5∶5的三种水凝胶。采用溶剂挥发法制备卡马西平-丁二酸药物共晶(carbamazepine-succinic acid,CBZ-SUC)。使用PVP-semi-IPN-PCL/PLA负载CBZ-SUC共晶,考察上述三种凝胶药物载体的载药能力及体外释放行为。使用1∶9、3∶7、5∶5比例凝胶制备了载药量分别为17%、19%、21%,包封率分别为71%、83%、89%的载药凝胶,其在37℃,pH=6.8 PBS溶液中体外释放效果均优于未使用凝胶载体的CBZ-SUC共晶。其中,3∶7组载药凝胶的累积释放量最高,溶解96h时累积释放量达到约70%。实验结果表明PVP-semi-IPN-PCL/PLA对CBZ-SUC药物共晶具有负载和控释能力,通过将药物共晶与凝胶药物载体两种手段相结合,能够抑制药物共晶的溶液介导相转变现象,为改善难溶性药物溶解行为,提高其生物利用度提供了一个有效手段。Polyvinylpyrrolidone-semi-interpenetrating network-polycaprolactone/poly(lactic acid)(PVP-semi-IPN-PCL/PLA)hydrogels were prepared through free radical polymerization of N-vinyl pyrrolidone(NVP)in ethyl acetate solution of PCL and PLA.Three kinds of PVP-semi-IPN-PCL/PLA hydrogels were prepared with the hydrophobic to hydrophilic ratio of 1:9,3:7,5:5,respectively.Carbamazepine-succinic acid(CBZ-SUC)cocrystal was prepared through evaporation method.PVP-semi-IPN-PCL/PLA hydrogels were used as drug vector for CBZ-SUC cocrystal delivery.The CBZ-SUC cocrystal loading and in vitro release abilities of PVP-semi-IPN-PCL/PLA hydrogels with different hydrophobic to hydrophilic ratios were studied.CBZ-SUC cocrystal loaded hydrogels were prepared with the drug loading capacity of 17%,19%,21%,encapsulation efficiency of 71%,83%,89%,respectively.The in vitro release of CBZ was studied in pH 6.8 PBS solution at 37℃,and the results show that the release profiles of hydrogels loaded CBZ cocrystal were better than those of CBZ cocrystal without hydrogels vector.The 3:7 hydrogel loaded CBZ cocrystal has the highest cumulative release amount,which reached about 70%when dissolved for 96 h.The results of this study show that PVP-semi-IPN-PCL/PLA hydrogels are capable of loading and control release of CBZ-SUC cocrystal.The combination of pharmaceutical cocrystal and hydrogel drug vector can restrain the solution mediated phase transition of cocrystal,which can be an effective way to improve the dissolution behavior and bioavailability of poorly soluble drugs.

关 键 词：PVP-semi-IPN-PCL/PLA水凝胶 药物载体 药物共晶 体外释放 

分 类 号：TQ460.1[化学工程—制药化工] TQ427.26