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醋酸曲安奈德微乳作为治疗葡萄膜炎的前瞻性眼用给药系统的研发:体外和体内评价

Development of Triamcinolone Acetonide-Loaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation.

作者信息

Mahran Alaa, Ismail Sayed, Allam Ayat A

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

Department of Pharmaceutics, Faculty of Pharmacy, Sphinx University, New Assiut City, Assiut 71515, Egypt.

出版信息

Pharmaceutics. 2021 Mar 25;13(4):444. doi: 10.3390/pharmaceutics13040444.

Abstract

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% , respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (-25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.

摘要

由于缺乏方便的眼科剂型,葡萄膜炎(即葡萄膜炎症)的治疗具有挑战性。这项工作旨在确定载有曲安奈德(TA)的微乳剂作为治疗葡萄膜炎的眼科给药系统的有效性。采用水滴定法构建不同的伪三元相图。使用油酸、聚氧乙烯蓖麻油(Cremophor EL)和丙二醇制备了12种微乳剂配方。在所有测试配方中,由油:表面活性剂-助表面活性剂(1:1):水(分别为15:35:50%)组成的F3配方被发现是稳定的,并且显示出可接受的pH值、粘度、电导率、液滴大小(211±1.4nm)和zeta电位(-25±1.7mV),并且在24小时内几乎完全体外药物释放。在实验性葡萄膜炎诱导的兔模型中评估了优化配方的体内性能,并与市售TA混悬液(即Kenacort-A)进行了局部或结膜下注射比较。通过临床检查、白细胞计数、蛋白质含量测量和组织病理学检查评估眼部炎症。与市售混悬液相比,所开发的载TA微乳剂在治疗葡萄膜炎方面显示出更高的治疗效率和患者依从性。因此,它可被视为控制葡萄膜炎的一种潜在眼部治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2ba/8064451/de6d3401c428/pharmaceutics-13-00444-g001.jpg

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