Abstract

Background

The combination therapy of Isotretinoin (ITR) and antibacterial formulations administered through topical route suffer from several limitations including reduced therapeutic efficacy and low patient-compliance.

Experiment

The present study aimed to develop biocompatible lipid-based mixed micelles of ITR in combination with Clindamycin phosphate (CLIN) employing self-assembly method to improve its skin delivery, photostability, biocompatibility and pharmacodynamic efficacy.

Results

The MTT assay and cellular uptake studies showed non-cytotoxic effect to HaCat cell lines. The zone of inhibition studies conducted in Propionibacterium acnes provides the first literature evidence to support the antimicrobial property of Isotretinoin and Tretinioin. The nano-sized carriers offered (19.3 ± 1.03 nm particle size with −3.12 mV zeta potential) enhanced permeation, skin retention, pre-clinical efficacy and significant skin biocompatibility. The testosterone-induced acne model proved superior pharmacodynamic efficacy of lab developed formulation vis-à-vis marketed products of both the drugs. The results were further confirmed by the histopathological studies of respective skin samples treated with different formulations.

Conclusion

The lab developed lipid-based micellar formulation of ITR and CLIN offers a better strategy for the combined delivery of unstable molecules like ITR and CLIN in acne management.

中文翻译：

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基于磷脂的混合胶束系统共同递送异维A酸和克林霉素赋予治疗寻常痤疮的协同作用

摘要

背景

通过局部途径给药的异维A酸（ITR）和抗菌制剂的联合治疗存在一些局限性，包括治疗效果降低和患者依从性低。

实验

本研究旨在开发生物相容性脂质基 ITR 混合胶束与克林霉素磷酸酯 (CLIN) 结合，采用自组装方法改善其皮肤递送、光稳定性、生物相容性和药效学功效。

结果

MTT 测定和细胞摄取研究表明对 HaCat 细胞系无细胞毒性作用。在痤疮丙酸杆菌中进行的抑菌圈研究提供了第一个支持异维甲酸和维甲酸抗菌特性的文献证据。提供的纳米级载体（19.3 ± 1.03 nm 粒径，-3.12 mV zeta 电位）增强了渗透性、皮肤保留、临床前功效和显着的皮肤生物相容性。睾酮诱导的痤疮模型证明了实验室开发的制剂与两种药物的市售产品相比具有优越的药效学功效。结果通过用不同制剂处理的各个皮肤样品的组织病理学研究进一步证实。

结论

该实验室开发了 ITR 和 CLIN 的基于脂质的胶束配方，为在痤疮管理中联合递送 ITR 和 CLIN 等不稳定分子提供了更好的策略。