原花青素在多孔薄膜中实现高效加载与长效释放的研究  

Efficient loading and long-term release of proanthocyanidins within the porous thin film

作　　者：王硕 张聪聪 姚晓敏 WANG Shuo;ZHANG Congcong;YAO Xiaomin(Zhejiang Pharmaceutical University,Ningbo 315100,China)

机构地区：[1]浙江药科职业大学,浙江宁波315100

出　　处：《药学研究》2023年第4期238-242,共5页Journal of Pharmaceutical Research

基　　金：浙江省骨科学重点实验室开放基金项目(No.ZJGK1806Y);宁波市自然科学基金(No.2019A610350)。

摘　　要：目的探讨了原花青素药物分子通过材料表面介导的方式实现长效扩散型释放行为的可能性。方法将原花青素分散在水中配制为药物溶液,与三氯甲烷共混后通过超声乳化的方式将混合液制备成为稳定的反相乳液。在高湿度环境条件下,将所制得的乳液浇筑在聚苯乙烯平面膜片上,待有机溶剂和水分挥发后获得表面和本体层均具有多孔结构的聚合物薄膜,并以此一步法实现原花青素在薄膜中的封装加载。最后将所制备得到的药物加载薄膜在磷酸缓冲盐溶液中浸泡进行药物释放试验,分时段取出缓冲液样品进行光谱表征确定原花青素的释放量,以此实现在28 d内对原花青素释放行为的跟踪表征。结果利用反相乳液浇筑致孔的方法,可以制备具有多层多孔结构的载药聚合物薄膜。经过乳液中水油比的调节,可以实现薄膜表层和本体层的多孔结构的调控。利用含水溶性荧光素乳液的浇筑成膜实验,并通过激光共聚焦显微镜结果证实了由反相乳液的乳液水滴所携带的亲水组分可以高效地实现在所形成多孔结构中的选择性分布,证明了原花青素组分在多孔膜当中可以实现有效加载。在这种多孔多层结构的薄膜当中所加载的原花青素可以实现超过28 d以上的长效缓释,其释放行为遵循了Fickian扩散式机理。结论利用聚合物多孔薄膜或者涂层作为药物载体,可以实现有效的药物加载和长效型释放,将能为设计高效灵活的药物释放体系提供有效的参考。Objective To evaluate the possibility of achieving long-term diffusion-based delivery of proanthocyanidins(PAC)via surface-mediated method.Methods PAC was dissolved in deionized water,and the PAC aqueous solution was mixed with chloroform.The mixture was then emulsified by using the ultrasonic emulsification instrument to make the inverse emulsion with PAC dispersed in the emulsion droplets.The as-prepared inverse emulsion was cast onto the flat film made from polystyrene under the environmental condition of high humidity.After complete solidification,the obtained film was rendered with multi-layered porous structure.Drug release profiling experiments were performed by immersing the PAC-loaded film in phosphate buffer saline(PBS).At the predetermined time-points,the PBS solutions were analyzed by ultraviolet-visible spectrophotometry to calculate the percentage of PAC release.Testing period lasted for 28 days.Results By using the inverse-emulsion casting method,PAC-loaded polymeric film with asymmetric multi-layered micro-porous structures was facilely prepared.Dynamic morphological manipulation on the created porous structures was achieved by tuning the composition of the casting emulsion.By using fluorescent probe combined with confocal laser scanning microscopy,the hydrophilic component was proved to be efficiently dispersed within the porous structures both in the surface and bulk layers.The PAC-loaded film samples with different features of multi-layered porous structures were proved to be able to achieve sustained drug release behavior for more than 28 days,following Fickian diffusion mechanism.Conclusion By the design of porous film or coating as drug carriers,the effective drug loading and long-lasting drug delivery could be achieved.It provides insight for the construction of an efficient and flexible drug delivery platform.

关 键 词：原花青素 多孔薄膜 长效释放 药物加载 

分 类 号：R284.1[医药卫生—中药学]