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Evaluation of Transdermal Transport and Concurrent Cutaneous Hydrolysis of Timolol Prodrug for the Treatment of Infantile Hemangiomas

文献类型：期刊论文

作者Chang, Shih-Jen2; Wang, Huiyuan1; Chen, Jialin2; Chen, Qianyi2; Chang, Lei2; Huang, Yongzhuo1; Qiu, Yajing2; Lin, Xiaoxi2
刊名PHARMACEUTICS
出版日期2022-08-01
卷号14期号:8页码:12
关键词infantile hemangioma timolol maleate butyryl timolol maleate prodrug sequelae hydrolysis
DOI10.3390/pharmaceutics14081607
通讯作者Qiu, Yajing(hedwig_qiu@live.cn) ; Lin, Xiaoxi(linxiaoxi@126.com)
英文摘要Infantile hemangiomas (IH) leave sequelae after involution. Topical application of timolol maleate (TM) is the mainstream treatment for superficial lesions but is limited by its low penetrable properties. We aimed to develop a superior skin permeation drug while maintaining the therapeutic properties of timolol. We predict that this drug will promote the involution of thick and deep IH lesions and avoid sequelae. We chemically modified drug structure to prepare butyryl timolol maleate (BT) prodrug and conducted in vitro and in vivo toxicity evaluations of BT with rat dorsal skin and normal skin cells. Skin permeation and absorption comparisons of TM and BT were conducted using rat and porcine skin models. Conversion efficiency of BT to timolol was also tested on human skin ex vivo. BT did not cause skin irritation on rat dorsal skin and exhibited low cytotoxicity overall. BT exhibited superior skin permeation ability compared with that of TM, whilst maintaining a low systemic absorbance. Further, BT was converted to timolol in human skin in a time-dependent manner. Noticeably, timolol accumulation in the skin from BT was higher than that from TM. Finally, BT demonstrated similar biocompatibility with TM in the IH tumor. BT enhances local delivery of timolol and its skin permeation. Using BT, we could eliminate thicker IH lesions that are prone to leave sequelae, and potentially help young children avoid dermal sequelae, disfigurement, and concomitant therapy.
WOS关键词TOPICAL TIMOLOL ; STEM-CELLS ; ENDOTHELIAL-CELLS ; PROPRANOLOL ; APOPTOSIS ; PERICYTES ; DELIVERY ; GEL
资助项目National Natural Science Foundation of China[81602786] ; Clinical Research Plan of SHDC[SHDC2020CR2036B]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者MDPI
WOS记录号WOS:000846999900001
源URL[http://119.78.100.183/handle/2S10ELR8/302126]  
专题新药研究国家重点实验室
通讯作者Qiu, Yajing; Lin, Xiaoxi
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Plast & Reconstruct Surg, Shanghai 200011, Peoples R China
推荐引用方式
GB/T 7714		 Chang, Shih-Jen,Wang, Huiyuan,Chen, Jialin,et al. Evaluation of Transdermal Transport and Concurrent Cutaneous Hydrolysis of Timolol Prodrug for the Treatment of Infantile Hemangiomas[J]. PHARMACEUTICS,2022,14(8):12.
APA Chang, Shih-Jen.,Wang, Huiyuan.,Chen, Jialin.,Chen, Qianyi.,Chang, Lei.,...&Lin, Xiaoxi.(2022).Evaluation of Transdermal Transport and Concurrent Cutaneous Hydrolysis of Timolol Prodrug for the Treatment of Infantile Hemangiomas.PHARMACEUTICS,14(8),12.
MLA Chang, Shih-Jen,et al."Evaluation of Transdermal Transport and Concurrent Cutaneous Hydrolysis of Timolol Prodrug for the Treatment of Infantile Hemangiomas".PHARMACEUTICS 14.8(2022):12.

入库方式： OAI收割

来源：上海药物研究所

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