School of Traditional Chinese Medicine, Southern Medical University, 1838, North Guangzhou Avenue, Guangzhou, 510515, China.
Drug Deliv Transl Res. 2024 Jun;14(6):1582-1600. doi: 10.1007/s13346-023-01473-x. Epub 2023 Nov 19.
Licorice flavonoids (LFs) are derived from perennial herb licorice and have been attaining a considerable interest in cosmetic and skin ailment treatments. However, some LFs compounds exhibited poor permeation and retention capability, which restricted their application. In this paper, we systematically investigated and compared the enhancement efficacy and mechanisms of different penetration enhancers (surfactants) with distinct lipophilicity or "heat and cool" characteristics on ten LFs compounds. Herein, the aim was to unveil how seven different enhancers modified the stratum corneum (SC) surface and influence the drug-enhancers-skin interaction, and to relate these effects to permeation enhancing effects of ten LFs compounds. The enhancing efficacy was evaluated by enhancement ratio (ER), ER, and ER, which was conducted on the porcine skin. It was summarized that heat capsaicin (CaP) and lipophilic Plurol® Oleique CC 497 (POCC) caused the most significance of SC lipid fluidity, SC water loss, and surface structure alterations, thereby resulting in a higher permeation enhancing effects than other enhancers. CaP could completely occupied drug-skin interaction sites in the SC, while POCC only occupied most drug-skin interactions. Moreover, the enhancing efficacy of both POCC and CaP was dependent on the log P values of LFs. For impervious LFs with low drug solubility, enhancing their drug solubility could help them permeate into the SC. For high-permeation LFs, their permeation was inhibited ascribed to the strong drug-enhancer-skin strength in the SC. More importantly, drug-surfactant-skin energy possessed a good negative correlation with the LFs permeation amount for most LFs molecules. Additionally, the activation of transient receptor potential vanilloid 1 (TRPV1) could enhance LFs permeation by CaP. The study provided novel insights for drug permeation enhancement from the viewpoint of molecular pharmaceutics, as well as the scientific utilization of different enhancers in topical or transdermal formulations.
甘草类黄酮（LFs）来源于多年生草本甘草，在化妆品和皮肤疾病治疗方面受到了相当大的关注。然而，一些 LFs 化合物表现出较差的渗透和保留能力，这限制了它们的应用。在本文中，我们系统地研究和比较了不同亲脂性或“热冷”特性的渗透增强剂（表面活性剂）对十种 LFs 化合物的增强效果和机制。本文旨在揭示七种不同的增强剂如何改变角质层（SC）表面，并影响药物-增强剂-皮肤相互作用，并将这些影响与十种 LFs 化合物的渗透增强效果联系起来。增强效果通过增强比（ER）、ER 和 ER 来评估，在猪皮上进行。结果表明，热辣椒素（CaP）和亲脂性 Plurol® Oleique CC 497（POCC）引起 SC 脂质流动性、SC 水分流失和表面结构改变最大，因此具有更高的渗透增强效果。CaP 可以完全占据 SC 中药物-皮肤相互作用的位置，而 POCC 只占据了大部分药物-皮肤相互作用的位置。此外，POCC 和 CaP 的增强效果都依赖于 LFs 的 log P 值。对于渗透性差、药物溶解度低的 LFs，提高其药物溶解度有助于其渗透进入 SC。对于高渗透性的 LFs，由于 SC 中药物-增强剂-皮肤的强度较强，其渗透受到抑制。更重要的是，对于大多数 LFs 分子，药物-表面活性剂-皮肤能量与 LFs 渗透量呈良好的负相关。此外，CaP 可以通过激活瞬时受体电位香草素 1（TRPV1）来增强 LFs 的渗透。该研究从药物传递的角度为药物渗透增强提供了新的见解，并为局部或透皮制剂中不同增强剂的科学利用提供了依据。
