胆汁酸对盐酸克林霉素皮肤渗透性的影响:体外和室内初步研究。

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Dragana Zaklan, Dušan Nešić, Darko Mitrović, Slavica Lazarević, Maja Đanić, Momir Mikov, Nebojša Pavlović
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引用次数: 0

摘要

背景和目的:克林霉素外用制剂被广泛应用于临床实践,但生物利用度低和皮肤渗透受限大大限制了其疗效。增强渗透性是克服传统外用药物制剂缺点的一种有前途的合理策略。我们的目的是通过在两个相关的 pH 值(5.5 和 6.5)下进行体外皮肤平行人工膜渗透性试验(skin-PAMPA),评估胆酸(CA)和脱氧胆酸(DCA)对盐酸克林霉素渗透性的影响,以及受试物质与皮肤 ATP 结合盒(ABC)转运体之间的相互作用:方法:培养期结束后,用分光光度法测定两个分区中盐酸克林霉素的浓度,并计算表观渗透系数(Papp)。使用维也纳 LiverTox 网络服务预测了克林霉素和胆汁酸与人体皮肤中潜在药物转运体的相互作用:结果:测试溶液中最高研究浓度为 100 μM 的 CA 和 DCA 都增加了盐酸克林霉素的皮肤-PAMPA 膜渗透性。这种效应在 CA 和较高的研究 pH 值 6.5 时更为明显,而这正是大多数使用局部克林霉素制剂治疗的皮肤病适应症的特征。克林霉素的转运也可能是由位于皮肤中的 ABC 转运体介导的,并在胆汁酸存在的情况下得到促进:本研究的结果为进一步研究使用胆汁酸作为增强渗透辅料的外用制剂的改进以及盐酸克林霉素的治疗效果奠定了坚实的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Influence of Bile Acids on Clindamycin Hydrochloride Skin Permeability: In Vitro and In Silico Preliminary Study.

Background and objective: Topical clindamycin formulations are widely used in clinical practice, but poor bioavailability and restricted skin penetration considerably limit their therapeutic efficacy. Penetration enhancement represents a promising and rational strategy to overcome the drawbacks of conventional topical pharmaceutical formulations. We aim to assess the influence of cholic acid (CA) and deoxycholic acid (DCA) on the permeability of clindamycin hydrochloride by performing the in vitro skin parallel artificial membrane permeability assay (skin-PAMPA) at two relevant pH values (5.5 and 6.5) and the interactions of tested substances with skin ATP-binding cassette (ABC) transporters in silico.

Methods: After the incubation period, the clindamycin hydrochloride concentrations in both compartments were determined spectrophotometrically, and the apparent permeability coefficients (Papp) were calculated. Vienna LiverTox web service was used to predict the interactions of clindamycin and bile acids with potential drug transporters located in human skin.

Results: Both CA and DCA at the highest studied concentration of 100 μM in the tested solutions increased the skin-PAMPA membrane permeability of clindamycin hydrochloride. This effect was more pronounced for CA and at a higher studied pH value of 6.5, which is characteristic of most dermatological indications treated with topical clindamycin preparations. Clindamycin transport may also be mediated by ABC transporters located in skin and facilitated in the presence of bile acids.

Conclusions: The results of this study provide a solid foundation for further research directed at the improvement of topical formulations using bile acids as penetration-enhancing excipients, as well as the therapeutic efficacy of clindamycin hydrochloride.

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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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