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电穿孔增强透皮给药:脂水分配系数、解离常数、溶解度和渗透时间的影响

Electroporation-enhanced transdermal drug delivery: Effects of logP, pK, solubility and penetration time.

作者信息

Chen Xiao, Zhu Lin, Li Ruiteng, Pang Lulu, Zhu Siqing, Ma Jinqiu, Du Lina, Jin Yiguang

机构信息

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China; Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.

出版信息

Eur J Pharm Sci. 2020 Aug 1;151:105410. doi: 10.1016/j.ejps.2020.105410. Epub 2020 Jun 4.

Abstract

Electroporation is an important physical technique to improve drug transdermal delivery, although its mechanism remains unclear. Here, some types of polar drugs, including aspirin, diclofenac sodium, metformin hydrochloride, ibuprofen and zidovudine, were used as the model drugs for the exploration of electroporation mechanisms. Electroporation had great influences on the structure of stratum corneum to improve the cumulative permeability due to the formation of pores maintaining for at least 2 h, depending on the power and time, and then the permeation gradually recovered to the normal value after 12 h. A mathematical model was firstly established to exhibit the relationship between the electroporation-improving cumulative permeation and the physiochemical properties of the model drugs, involving oil-water partition coefficient (logP), dissociation constant (pKa) and solubility (S). Increased cumulative permeation depended on increased S, decreased logP and pKa. Electroporation is an effective physical technique to improve transdermal drug delivery depending on itself and the properties of drugs.

摘要

电穿孔是一种改善药物经皮递送的重要物理技术,尽管其机制尚不清楚。在此,包括阿司匹林、双氯芬酸钠、盐酸二甲双胍、布洛芬和齐多夫定在内的某些类型的极性药物被用作探索电穿孔机制的模型药物。电穿孔对角质层结构有很大影响,由于形成了至少维持2小时的孔,这取决于功率和时间,从而提高了累积渗透率,然后在12小时后渗透率逐渐恢复到正常值。首先建立了一个数学模型来展示电穿孔改善累积渗透率与模型药物理化性质之间的关系,这些理化性质包括油水分配系数(logP)、解离常数(pKa)和溶解度(S)。累积渗透率的增加取决于S的增加、logP和pKa的降低。电穿孔是一种有效的物理技术,可根据其自身以及药物的性质来改善经皮给药。

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