Design and fabrication of r-hirudin loaded dissolving microneedle patch for minimally invasive and long-term treatment of thromboembolic disease  

作　　者：Mengfang Wu Tian Xia Yaran Li Tianfa Wang Shijia Yang Jinchao Yu Qiaoyan Liang Teng Shen Min Yu Bing Zhao 

机构地区：[1]Key Laboratory of Metabolism and Molecular Medicine,Ministry of Education,Fudan University,Shanghai 200032,China [2]The Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China [3]Key Laboratory of Smart Drug Delivery,Ministry of Education,Department of Pharmaceutics,School of Pharmacy,Fudan University,Shanghai 201203,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第2期284-297,共14页亚洲药物制剂科学（英文）

基　　金：supported by the National Natural Science Foundation of China (NSFC 81902995);the project funded by China Postdoctoral Science Foundation (2018M641936)

摘　　要：Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous(SC)and intravenous(IV)administration,but there is a risk of haemorrhage via SC and IV.Thus,microneedle(MN)provides painless and sanitary alternatives to syringes and oral administration.However,the current technological process for the micro mould is complicated and expensive.The micro mould obtained via three-dimensional(3D)printing is expected to save time and cost,as well as provide a diverse range of MNs.Therefore,we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch.The results show that r-hirudin-loaded and hyaluronic acid(HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models.These results indicate that based on 3D printing technology,MNs combined with r-hirudin are expected to achieve diverse customizableMNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.

关 键 词：ANTICOAGULANT r-hirudin Microneedle patch 3D printing technology 

分 类 号：R943[医药卫生—药剂学]