Purpose

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.

Methods

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.

Results

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_last 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.

Conclusions

An unconventional passive enhancement of transdermal drug delivery was achieved via improving PEs themselves releasing from acrylic pressure-sensitive adhesive.

Influence of PEs release behavior on drug permeation through skin and molecular mechanism

中文翻译：

---

透皮给药的非常规被动增强：从丙烯酸压敏胶的释放中获得对渗透增强剂的机械理解。

目的

增强功效的渗透促进剂（PEs）取决于两个过程：PE从斑块中释放出来并作用于皮肤。与它们对皮肤的作用相比，人们对PE的释放过程了解甚少。因此，本研究的目的是对从贴剂的丙烯酸压敏胶粘剂中释放PE的机理进行了解，并提出非常规的PE功效增强方法。

方法

在药物渗透研究和药物药代动力学研究中都评估了PE的功效。共焦拉曼光谱法通过绘制皮肤中PE的动态分布图来观察PE的释放行为。分别通过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提供了PEs释放行为的机理。

结果

PE本身的释放行为极大地限制了它们的功效。通过使用PEG 400，油酸的改善（OA）的释放行为达到了，和OA的疗效增强比（被显著增强ER）从2.69至4.10和AUC_最后从1574±87 2664±249纳克·H / mL，分别。OA释放行为的改善主要是由于OA和粘合剂之间相互作用的减少，这是由其他具有与粘合剂形成氢键能力强的小分子引起的。而且，粘合剂的刚性是影响PEs释放行为的因素。

结论

通过改善PE自身从丙烯酸压敏胶粘剂中的释放，可以实现透皮给药的非常规被动增强。

PEs释放行为对皮肤药物透过和分子机制的影响