We previously developed two optimized formulations of dexamethasone acetate (DXMa) hydrogels by means of special cubic mixture designs for topical ocular administration. These gels were elaborated with hydroxypropyl-β-CD (HPβCD) and hydroxypropyl-γ-CD (HPγCD) and commercial hydrogels in order to enhance DXMa water solubility and finally DXMa’s ocular bioavailability and transcorneal penetration. The main objective of this study was to characterize them and to evaluate in vitro, ex vivo, and in vivo their safety, biopermanence, and transcorneal permeation. Gels A and B are Newtonian fluids and display a viscosity of 13.2 mPa.s and 18.6 mPa.s, respectively, which increases their ocular retention, according to the in vivo biopermanence study by PET/CT. These hydrogels could act as corneal absorption promoters as they allow a higher transcorneal permeation of DXMa through porcine excised cornea, compared to DEXAFREE^® and MAXIDEX^®. Cytotoxicity assays showed no cytotoxic effects on human primary corneal epithelial cells (HCE). Furthermore, Gel B is clearly safe for the eye, but the effect of Gel A on the human eye cannot be predicted. Both gels were also stable 12 months at 25 °C after sterilization by filtration. These results demonstrate that the developed formulations present a high potential for the topical ocular administration of dexamethasone acetate.

中文翻译：

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基于地塞米松醋酸酯的水凝胶结合羟丙基环糊精和多糖进行眼部递送的生物药物评估。

我们以前通过特殊的立方混合物设计开发了两种优化的醋酸地塞米松（DXMa）水凝胶制剂，用于局部眼部给药。这些凝胶分别用羟丙基-β-CD（HPβCD）和羟丙基-γ-CD（HPγCD）和市售水凝胶制成，以增强DXMa的水溶性，并最终增强DXMa的眼部生物利用度和经角膜穿透性。这项研究的主要目的是表征它们，并在体外，离体和体内评估其安全性，生物持久性和透角膜渗透性。凝胶A和B是牛顿流体，根据体内显示，其粘度分别为13.2 mPa.s和18.6 mPa.s，这会增加它们的眼保持力。PET / CT的生物持久性研究。因为它们允许这些水凝胶可以作为角膜吸收促进更高DXMa的transcorneal渗透通过猪角膜切除相比，DEXAFREE ^®和MAXIDEX ^®。细胞毒性测定显示对人原代角膜上皮细胞（HCE）无细胞毒性作用。此外，凝胶B显然对眼睛安全，但是无法预测凝胶A对人眼的作用。通过过滤灭菌后，两种凝胶在25°C下也稳定12个月。这些结果表明，所开发的制剂对于乙酸地塞米松的局部眼内给药具有很高的潜力。