Purpose

Topical corticosteroids administration is commonly used for management of various ocular conditions especially those affecting the anterior segment of the eye. Poor solubility and limited pre-corneal residence time result in insufficient drug penetration to the outer (cornea and conjunctival-scleral) coats of the eye. This study aimed to prepare and evaluate cubosomes for prolonging residence time and enhancing ocular bioavailability of BDP.

Methods

GMO-cubosomes were prepared using the top-down technique. Two stabilizers were investigated: poloxamer 407 and solulan C24. Particle size, EE %, polarized-light microscopy, TEM, in vitro release, transcorneal permeation, BCOP, histopathology and in vivo evaluation for treatment of uveitis in a rabbits’ model were studied.

Results

The prepared cubosomes were of nano-sizes (100 nm – 278 nm); EE% was around 94%. The cubosomes were confirmed by visualizing the “Maltese crosses” textures. Transcorneal permeation was significantly (p < 0.05) improved, compared to BDP-suspension (the control formulation). The optimized cubosomes F1P was incorporated in CMC gel (Cubo-gel). The prepared Cubo-gel formulations showed better rheological characteristics and high ocular tolerability. Superior anti-inflammatory properties were recorded for the Cubo-gel for treatment of endotoxin-induced uveitis in the rabbit model when compared to the control BDP-suspension.

Conclusions

Transcorneal permeation parameters P_app and flux and AUC_0-10h markedly enhanced by up to 4-, 5.8-and 5.5-fold respectively, compared to the control BDP-suspension formulation. This study suggested that cubosomes/Cubo-gel could be an auspicious ocular delivery system for BDP that was able to effectively treat uveitis (a disease of the posterior segment of the eye).

中文翻译：

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用于眼部递送丙酸倍氯米松的葡萄球菌/脂质体凝胶的制备和评价，用于治疗葡萄膜炎。

目的

局部使用皮质类固醇激素通常用于治疗各种眼部疾病，尤其是影响眼前节的眼部疾病。不良的溶解度和有限的角膜前停留时间导致药物无法充分渗透到眼的外层（角膜和结膜-巩膜）。这项研究的目的是准备和评估立方糖体，以延长其停留时间并增强BDP的眼部生物利用度。

方法

使用自上而下的技术制备了GMO立方体。研究了两种稳定剂：泊洛沙姆407和solulan C24。研究了粒径，EE％，偏光显微镜，TEM，体外释放，经角膜渗透，BCOP，组织病理学和体内评价在兔模型中治疗葡萄膜炎的研究。

结果

制备的立方微粒为纳米级（100 nm – 278 nm）；EE％约为94％。通过可视化“马耳他十字”纹理来确认小立方体。 与BDP悬浮液（对照制剂）相比，经角膜渗透性显着改善（p <0.05）。将优化的立方脂质体F1P掺入CMC凝胶（Cubo-gel）中。制备的Cubo-gel配方具有更好的流变特性和较高的眼耐受性。与对照BDP悬浮液相比，Cubo-gel在兔子模型中记录了优异的抗炎特性，可用于治疗内毒素诱导的葡萄膜炎。

结论

与对照BDP悬浮液制剂相比，经_角膜渗透参数P _app和通量以及AUC _0-10h分别显着提高了4倍，5.8倍和5.5倍。这项研究表明，cubosomes / Cubo-gel可能是BDP的吉祥眼部递送系统，能够有效治疗葡萄膜炎（眼后段疾病）。