Topical ocular drug administration aimed at providing a high drug concentration at the precorneal site accompanied with enhanced corneal permeability to avoid systemic side effects is a very important therapeutic goal in ocular disorder therapy. In the present study, the solubility of the poorly soluble drug celecoxib (CXB) was significantly improved using a facile strategy to generate a high drug payload micellar formulation. By varying the drug/polymer feed ratios, the mean diameter of the formed CXB micelles ranged from 21.34 ± 0.23 to 28.53 ± 0.11 nm, and the drug loading capacity ranged from 4.31 to 15.87%. Transmission electron microscopy (TEM) showed that the formed CXB micelles had a uniform spherical morphology. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the physicochemical properties of lyophilized CXB micelles. The obtained CXB micelles retained their properties through freeze-drying and rehydration, thereby providing long-term physicochemical stability over 3 months of storage at -20 °C. An in vitro release study showed that the CXB micelles released CXB in a sustained release manner without any apparent burst release over 72 h by the Higuchi non-Fickian diffusion mechanism. Notably, using corneas excised from rabbits, the in vitro corneal permeability of CXB from the micellar formulation was observed to be significantly greater than that of the microparticle formulation. Overall, the proposed micelles might be a promising vehicle for ophthalmic delivery of CXB with the significant enhancement of water solubility and corneal permeability.

中文翻译：

---

产生高载药量塞来昔布胶束以增强角膜通透性的简便策略。

旨在在角膜前位点提供高药物浓度并增强角膜通透性以避免全身性副作用的局部眼用药物给药是眼病治疗中非常重要的治疗目标。在本研究中，使用简便的策略生成高药物有效载荷胶束制剂，可显着改善难溶性药物塞来昔布（CXB）的溶解度。通过改变药物/聚合物的进料比，所形成的CXB胶束的平均直径为21.34±0.23至28.53±0.11nm，并且载药量为4.31至15.87％。透射电子显微镜（TEM）显示形成的CXB胶束具有均匀的球形形态。差示扫描量热法（DSC）X射线粉末衍射（XRD）和傅里叶变换红外光谱（FTIR）用于表征冻干的CXB胶束的理化性质。所获得的CXB胶束通过冷冻干燥和再水化保留了它们的特性，从而在-20°C下储存3个月提供了长期的理化稳定性。体外释放研究表明，CXB胶束通过Higuchi非Fickian扩散机制在72小时内以持续释放的方式释放CXB，而没有任何明显的爆发释放。值得注意的是，使用从兔子切下的角膜，观察到来自胶束制剂的CXB的体外角膜渗透性显着大于微粒制剂的CXB。总体，