Topical tacrolimus nanocapsules eye drops for therapeutic effect enhancement in both anterior and posterior ocular inflammation models.
Topical tacrolimus nanocapsules eye drops for therapeutic effect enhancement in both anterior and posterior ocular inflammation models.
复制标题
局部他克莫司纳米胶囊滴眼液在眼前部和后部炎症模型中的治疗效果增强。
DOI：
10.1016/j.jconrel.2021.03.035
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发表时间：
2021-05-10
期刊：
影响因子：
--
通讯作者：
Benita S
中科院分区：
文献类型：
--
作者：
Rebibo L;Tam C;Sun Y;Shoshani E;Badihi A;Nassar T;Benita S
他克莫司对眼部炎症有疗效。然而，由于药物的不稳定性，将其配制成稳定的眼科产品仍然是一个挑战。设计了负载他克莫司的纳米胶囊（NCs）用于眼滴注。进一步分析了该配方在不同实验条件下的稳定性和效果。理化性质表明纳米颗粒尺寸均匀，包封效率高。此外，冻干制剂在ICH长期储存和加速储存条件下分别稳定至少18个月和3个月。他克莫司NCs在单次和多次给药后均未引起家兔眼部刺激。此外，对分离的猪角膜进行的离体渗透试验和对不同兔子眼室的药代动力学分析表明，与溶解在油中的游离药物相比，NCs在保留和渗透到眼睛前房方面具有优势。此外，在大鼠眼内多剂量滴注NCs后，他克莫司在眼内的浓度很高，而血浆浓度很低。最后，开发的递送系统在小鼠角膜炎模型（前房炎症）中实现了四种典型炎症标志物的显著减少。此外，这些NCs作为滴眼液，在小鼠主要后房炎症模型，实验性自身免疫性葡萄膜炎中显示出临床和组织学疗效。
Tacrolimus has shown efficacy in eye inflammatory diseases. However, due to the drug lability, its formulation into a stable ophthalmic product remains a challenge. Tacrolimus-loaded nanocapsules (NCs) were designed for ocular instillation. Further, the stability and effects of the formulation were analyzed under different experimental conditions. Physicochemical characterization of the NCs revealed suitable homogeneous size and high encapsulation efficiency. Moreover, the lyophilized formulation was stable at ICH long term and accelerated storage conditions, for at least 18 and 3 months, respectively. The tacrolimus NCs did not elicit any eye irritation in rabbits after single- and multiple-dose applications. Additionally, ex vivo penetration assays on isolated porcine cornea and pharmacokinetics analyses in various rabbit eye compartments demonstrated the superiority of the NCs in retention and permeation into the anterior chamber of the eye compared to the free drug dissolved in oil. Moreover, multiple dose ocular instillation of the NCs in rats allowed high tacrolimus levels in the eye with very low plasma concentrations. Finally, the developed delivery system achieved a significant decrease in four typical inflammatory markers in a murine model of keratitis, an anterior chamber inflammation. Furthermore, these NCs, applied as eye drops, displayed clinical and histological efficacy in the mainly posterior chamber inflammation model of murine, experimental autoimmune uveitis.
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影响因子：
2.7
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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