Objective: To prepare everolimus nanoformulations and increase their solubility to suit their application in the eye. Methods: The everolimus micelles was prepared by thin film dispersion method using Tween-80 (P80) and polyoxyethylene stearate (P40S) as carriers. In addition, the everolimus nanosuspension was prepared by injection method using poloxamer 407 (P407), hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) as stabilizers. It was characterized in terms of particle size, PDI and encapsulation efficiency or drug loading. The in vitro release and in vitro rabbit scleral permeability characteristics were investigated, and the pharmacokinetics of anterior chamber drug in rabbit eyes were studied. Results: The average particle size of the micelles was (8.74 ± 0.21) nm, the encapsulation efficiency and drug loading were (90.12 ± 1.18)% and (2.14 ± 0.028)%, while the average particle size of the nanosuspension was (156.47 ± 1.10) nm, and the drug loading was (16.51 ± 0.21)%, respectively. Both in vitro release and rabbit scleral permeation models were consistent with the Higuchi equation. The pharmacokinetic experiments of aqueous humor showed that area under the curve of everolimus nanosuspension was about 3 times higher than that of micelles. Micelles could be achieved in the eye and maintained for a long time. Conclusion: The preparation of everolimus micelles or nanosuspension for eye are suitable for ocular administration and expected to be new dosage form for corneal transplantation immunological rejection or other ocular disease.

中文翻译：

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依维莫司的两种眼科纳米制剂的制备和研究。

目的：制备依维莫司纳米制剂并增加其溶解度以适合其在眼中的应用。方法：以Tween-80（P80）和聚氧乙烯硬脂酸酯（P40S）为载体，通过薄膜分散法制备依维莫司胶束。此外，依维莫司纳米混悬剂是通过使用泊洛沙姆407（P407），羟丙基甲基纤维素（HPMC）和聚乙烯醇（PVA）作为稳定剂的注射方法制备的。它通过粒径，PDI和包封效率或载药量来表征。研究了兔巩膜的体外释放和体外通透性，并研究了前房药物在兔眼中的药代动力学。结果：胶束的平均粒径为（8.74±0.21）nm，包封效率和载药量为（90.12±1。纳米悬浮液的平均粒径为（156.47±1.10）nm，分别为18）％和（2.14±0.028）％，药物载量分别为（16.51±0.21）％。体外释放和兔巩膜渗透模型均与Higuchi方程式一致。房水的药代动力学实验表明，依维莫司纳米混悬剂曲线下面积比胶束高约3倍。胶束可以在眼中获得并维持很长时间。结论：眼用依维莫司胶束或纳米混悬剂的制备适合眼部给药，有望成为角膜移植免疫排斥反应或其他眼部疾病的新剂型。21）％。体外释放和兔巩膜渗透模型均与Higuchi方程式一致。房水的药代动力学实验表明，依维莫司纳米混悬剂曲线下面积比胶束高约3倍。胶束可以在眼中获得并维持很长时间。结论：眼用依维莫司胶束或纳米混悬剂的制备适合眼部给药，有望成为角膜移植免疫排斥反应或其他眼部疾病的新剂型。21）％。体外释放和兔巩膜渗透模型均与Higuchi方程式一致。房水的药代动力学实验表明，依维莫司纳米混悬剂曲线下面积比胶束高约3倍。胶束可以在眼中获得并维持很长时间。结论：眼用依维莫司胶束或纳米混悬剂的制备适合眼部给药，有望成为角膜移植免疫排斥反应或其他眼部疾病的新剂型。胶束可以在眼中获得并维持很长时间。结论：眼用依维莫司胶束或纳米混悬剂的制备适合眼部给药，有望成为角膜移植免疫排斥反应或其他眼部疾病的新剂型。胶束可以在眼中获得并维持很长时间。结论：眼用依维莫司胶束或纳米混悬剂的制备适合眼部给药，有望成为角膜移植免疫排斥反应或其他眼部疾病的新剂型。