Progesterone (PG) may provide protection to the retina during retinitis pigmentosa, but its topical ocular supply is hampered by PG poor aqueous solubility and low ocular bioavailability. The development of efficient topical ocular forms must face up to two relevant challenges: Protective barriers of the eyes and lack of validated ex vivo tests to predict drug permeability. The aims of this study were: (i) To design micelles using Pluronic F68 and Soluplus copolymers to overcome PG solubility and permeability; and (ii) to compare drug diffusion through the cornea and sclera of three animal species (rabbit, porcine, and bovine) to investigate interspecies differences. Micelles of Pluronic F68 (3–4 nm) and Soluplus (52–59 nm) increased PG solubility by one and two orders of magnitude, respectively and exhibited nearly a 100% encapsulation efficiency. Soluplus systems showed in situ gelling capability in contrast to the low viscosity Pluronic F68 micelles. The formulations successfully passed the hen’s egg-chorioallantoic membrane test (HET-CAM) test. PG penetration through rabbit cornea and sclera was faster than through porcine or bovine cornea, although the differences were also formulation-dependent. Porcine tissues showed intermediate permeability between rabbit and bovine. Soluplus micelles allowed greater PG accumulation in cornea and sclera whereas Pluronic F68 promoted a faster penetration of lower PG doses.

中文翻译：

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用于局部眼部给药的孕酮胶束：活体眼通透性的种间和组织间差异。

孕酮（PG）可能在色素性视网膜炎期间为视网膜提供保护，但PG的水溶性差且眼生物利用度低，阻碍了其局部眼部供应。有效的局部眼用形式的发展必须面对两个相关的挑战：眼睛的保护性屏障以及缺乏可预测药物渗透性的有效体外试验。这项研究的目的是：（i）使用Pluronic F68和Soluplus共聚物设计胶束，以克服PG的溶解性和渗透性；（ii）比较三种动物（兔子，猪和牛）通过角膜和巩膜的药物扩散情况，以研究种间差异。Pluronic F68（3-4 nm）和Soluplus（52-59 nm）的胶束分别将PG的溶解度提高了一个和两个数量级，并表现出近100％的包封效率。与低粘度的Pluronic F68胶束相比，Soluplus系统显示出原位胶凝能力。该制剂成功通过了鸡蛋卵绒膜尿囊膜测试（HET-CAM）测试。PG通过兔角膜和巩膜的渗透速度比通过猪或牛角膜的渗透速度要快，尽管差异也取决于制剂。猪组织显示出兔和牛之间的中等渗透性。Soluplus胶束使角膜和巩膜中的PG积累更多，而Pluronic F68促进了较低PG剂量的更快渗透。PG通过兔角膜和巩膜的渗透速度比通过猪或牛角膜的渗透速度要快，尽管差异也取决于制剂。猪组织显示出兔和牛之间的中等渗透性。Soluplus胶束使角膜和巩膜中的PG积累更多，而Pluronic F68促进了较低PG剂量的更快渗透。PG通过兔角膜和巩膜的渗透比通过猪或牛角膜的渗透要快，尽管差异也取决于制剂。猪组织显示出兔和牛之间的中等渗透性。Soluplus胶束使角膜和巩膜中的PG积累更多，而Pluronic F68促进了较低PG剂量的更快渗透。