经扩散法载门冬胰岛素的相转化微针的制备与性能研究  

Preparation and Performance Investigation of Phase-transition Microneedles Loaded with Insulin Aspart via Diffusion Method

作　　者：朱琳[1] 张伟捷 张雨星 吴飞[1] 金拓[1] ZHU Lin;ZHANG Weijie;ZHANG Yuxing;WU Fei;JIN Tuo(School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240)

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》2024年第1期66-74,共9页Chinese Journal of Pharmaceuticals

摘　　要：基于聚乙烯醇(PVA)的相转化微针可利用溶胀形成的孔隙载药,在生物大分子药物递送上具有潜力。然而,经传统预混法制备的载药微针中的药物在微针根部和中心也有分布,造成药物在释放过程中的扩散距离较长,且难以穿透水凝胶网状基质,限制了药物的生物利用度。因此,该研究采用扩散法载药,并优化了PVA溶液与辅料(羧甲纤维素钠和葡聚糖)溶液的质量比,以提高载药量、释药率和表皮渗透性。结果显示,当PVA溶液与辅料溶液的质量比为3∶1、固形物含量为17.8%时,微针的溶胀性能较高且机械性能强,可有效递送药物至真皮层。以门冬胰岛素为模型药物时,相比传统预混法(透皮率不到25%),扩散法载药微针的透皮率可达31.0%~34.6%,体外释放率最高达93%。该研究中以扩散法制备的载药微针可提高亲水性大分子药物的释放率和生物利用度,为透皮给药系统的研发提供新策略。Polyvinyl alcohol(PVA)-based phase-transition microneedles can be utilized to load drugs through pores formed by swelling,and are highly promising for biomolecular drug delivery.However,due to the drug distribution at the root and center of drug-loaded microneedles prepared by the conventional premixing method,the diffusion distance during drug release is large and penetration through the hydrogel network matrix is dificult,which limit the bioavailability of the drug.Therefore,the diffusion method was used for protein drug-loading and the mass ratio of PVA solution to excipient(sodium carboxymethylcellulose and dextran)solution was optimized to improve the drug loading,drug release rate,and epidermal permeability.The results showed that when the mass ratio of PVA solution to excipient solution was 3:1 and the solid content was 17.8%,the microneedles had high swelling properties and strong mechanical properties,and could effectively deliver the drug to the dermis.Using insulin aspart as a model drug,compared with the traditional premixing method(the transdermal delivery rate was less than 25%),the transdermal delivery rate of drug-loaded microneedles prepared by the diffusion method could reach 31.0%-34.6%,and the in vitro release rate was up to 93%.The drug-loaded microneedles prepared by the diffusion method can improve the release rate and bioavailability of hydrophilic macromolecules,providing a new strategy for the development of transdermal drug delivery systems.

关 键 词：相转化微针 扩散法 门冬胰岛素 体外释放 体外透皮 

分 类 号：R944.9[医药卫生—药剂学]