用于微针贴剂快速体外评价的电纺丝纤维真皮层模型  

Electrospun Fiber Dermal Model for Rapid in vitro Evaluation of Microneedle Patch

作　　者：沈炎冰[1] 朱嗣文 吴飞[1] 金拓[1] 

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《中国医药工业杂志》2017年第10期1474-1478,共5页Chinese Journal of Pharmaceuticals

摘　　要：微针透皮贴剂已成为最有可能实现生物药高效、精准的非注射给药的在研制剂。微针贴剂高效透皮给药的机制在于长度小于1 mm的微针点阵可穿透药物透皮吸收的主要障碍——表皮,将药物释放于真皮。这一机制下,表皮不再是药物透皮吸收的律速步骤,药物在真皮层的扩散成为影响系统给药的关键环节。目前所有透皮释药的体外评价模型均以透过表皮为动力学障碍,不适合用来评价微针透皮贴剂。本研究旨在开发能够反映微针贴剂透皮给药时,药物在真皮层中的扩散动力学特征的体外快速评价模型。根据真皮层体液的动态特点设计了聚乙烯醇电纺纤维膜的真皮层模型,并进一步优化膜的厚度及微晶交联度,在体外试验中模拟出了赖脯胰岛素相转化微针透皮贴剂在模型猪上的血药浓度曲线。结果显示:厚0.5 mm并经1次冷冻-解冻处理实现微晶交联的聚乙烯醇电纺纤维膜模拟效果最好,可用作快速评价微针贴剂的体外模型。Microneedle patch is recognized to be a promising dosage form with the development for efficient and accurate transdermal delivery of biologic medicines. The array of small needles, less than 1 mm in length, may penetrate epidermis, the major resistance of transdermal absorption of drugs, and release their loads at the dermis layer. Under this mechanism, diffusion across the epidermis is no longer the rate-limiting step of drug absorption, and diffusion of the drug across the dermis layer becomes the key step affecting systemic drug administration. The models currently used for in vitro evaluation oftransdermal drug delivery are established on the epidermis barrier and are therefore invalid. The present study is therefore aimed to develop a new in vitro model for transdermal drug development using microneedle patches. We therefore designed a polyvinyl alcohol （PVA） fiber membrane made by electrospinning to mimic the dynamics of the interstitial fluids. By optimizing the membrane thickness and PVA microcrystalline domain density, we had successfully simulated the insulin lispro release profiles highly mimicking the in vivo pharmacokinetic profiles obtained in pig models. The optimized membrane thickness was 0.5 mm and microcrystalline domains were formed by one freeze-thaw cycle. The experimental results confirmed the feasibility of using PVA fiber membrane as an artificial dermis layer for rapid evaluation of microneedle patches.

关 键 词：微针 赖脯胰岛素 电纺纤维膜 人工真皮层 透皮 体外评价 

分 类 号：R944.9[医药卫生—药剂学]