Development and Evaluation of Cyclosporine a Mixed Micelle Eye Drops for Enhanced Ocular Drug Delivery

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2025-05-16 DOI:10.1208/s12249-025-03129-0

Yue Hu, Jiong Wu, Xiaoyan Du, Yan Shen, Daquan Chen, Xiujuan Feng, Dilei Yan

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Abstract

Ocular drug delivery is hindered by anatomical and physiological barriers that limit drug bioavailability. Among emerging solutions, mixed micelle systems offer promising potential for enhancing the efficacy of ocular formulations. This study investigates the development and evaluation of a novel cyclosporine A (CsA) micellar eye drop formulation using octylphenol polyethylene glycol ether 40 (OP-40), a surfactant with favorable ocular delivery properties, and polyoxyethylene hydrogenated castor oil 40 (RH-40), a non-ionic surfactant that can enhance the dispersion and stability of the system. OP-40 was optimized through a purification process, and a hybrid micelle system was developed by screening excipients and refining the formulation process. The critical micelle concentration (CMC), crystalline form of CsA, interactions between surfactants and excipients, and the influence of excipients on buffer capacity were systematically examined. The resulting eye drops demonstrated favorable physicochemical characteristics, including pH, osmolality, and stability under both accelerated conditions and long-term storage at room temperature. Furthermore, the formulation exhibited no ocular irritation in rabbit models, confirming its safety. In conclusion, OP-40-based CsA mixed micelle eye drops provide a promising strategy to overcome ocular drug delivery challenges, with significant potential to enhance bioavailability and therapeutic efficacy in ophthalmic applications.

Graphical Abstract

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环孢素a混合胶束滴眼液的研制与评价

眼部给药受到解剖和生理障碍的阻碍，这些障碍限制了药物的生物利用度。在新兴的解决方案中，混合胶束系统为提高眼部配方的功效提供了有希望的潜力。本研究研究了环孢素a （CsA）胶束滴眼液配方的研制和评价，该配方采用具有良好眼部给药性能的表面活性剂辛基酚聚乙二醇醚40 （OP-40）和增强体系分散性和稳定性的非离子表面活性剂聚氧乙烯氢化蓖麻油40 （RH-40）。通过纯化工艺对OP-40进行了优化，并通过辅料筛选和配方工艺优化，建立了混合胶束体系。系统考察了临界胶束浓度（CMC）、CsA的晶型、表面活性剂与赋形剂的相互作用以及赋形剂对缓冲容量的影响。所制备的滴眼液在加速条件和室温长期储存条件下均表现出良好的物理化学特性，包括pH值、渗透压和稳定性。此外，该配方在家兔模型中无眼部刺激，证实了其安全性。综上所述，基于op -40的CsA混合胶束滴眼液为克服眼部给药挑战提供了一种很有前景的策略，在眼科应用中具有提高生物利用度和治疗效果的巨大潜力。图形抽象

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.