Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People's Republic of China.
Department of Pharmaceutical Chemistry, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People's Republic of China.
Pharm Res. 2020 Aug 13;37(9):169. doi: 10.1007/s11095-020-02901-0.
Penetration enhancers (PEs) enhancing efficacy depends on two processes: PEs release from patches and action on skin. Compared with their action on skin, PEs release process was poorly understood. Therefore, the purpose of this study was to make a mechanistic understanding of PEs release from acrylic pressure-sensitive adhesive of patches and propose an unconventional enhancement of PEs efficacy.
PEs efficacy was evaluated both in drug permeation study and drug pharmacokinetic study. Confocal Raman spectroscopy was employed to observe PEs release behavior by mapping PEs dynamic distribution in skin. The mechanism of PEs release behavior was provided from molecular interaction and rheology using FT-IR, molecular docking, molecular dynamic simulation and rheometer, separately.
The release behavior of PEs themselves greatly restricted their efficacy. By using PEG 400, an improvement of oleic acid (OA) release behavior was achieved, and the efficacy of OA was significantly enhanced with enhancing ratio (ER) from 2.69 to 4.10 and AUC from 1574 ± 87 to 2664 ± 249 ng·h/mL, separately. The improvement of OA release behavior was primarily resulted from reduction of the interaction between OA and adhesive, which was caused by other small molecules with a strong ability in forming hydrogen bonds with adhesive. Also, the rigidity of adhesive was a factor in affecting PEs release behavior.
An unconventional passive enhancement of transdermal drug delivery was achieved via improving PEs themselves releasing from acrylic pressure-sensitive adhesive. Graphical abstract Influence of PEs release behavior on drug permeation through skin and molecular mechanism.
渗透促进剂（PEs）的疗效取决于两个过程：PEs 从贴剂中释放和在皮肤上的作用。与它们在皮肤上的作用相比，PEs 的释放过程了解甚少。因此，本研究的目的是从贴剂的丙烯酸压敏胶中对 PEs 的释放过程进行深入了解，并提出一种非常规的增强 PEs 疗效的方法。
通过绘制 PEs 在皮肤中的动态分布，利用共焦拉曼光谱观察 PEs 的释放行为，评估 PEs 的药效。分别采用傅里叶变换红外光谱（FT-IR）、分子对接、分子动力学模拟和流变仪，从分子相互作用和流变学的角度，提供 PEs 释放行为的机制。
PEs 本身的释放行为极大地限制了它们的疗效。通过使用 PEG400，可以改善油酸（OA）的释放行为，OA 的疗效显著增强，增强比（ER）从 2.69 增加到 4.10，AUC 从 1574±87 增加到 2664±249ng·h/mL。OA 释放行为的改善主要是由于 OA 与胶黏剂之间相互作用的减弱，这是由于具有较强氢键形成能力的其他小分子引起的。此外，胶黏剂的刚性也是影响 PEs 释放行为的一个因素。
通过改善 PEs 从丙烯酸压敏胶中的释放，可以实现经皮给药的非传统被动增强。
