Corneal penetration is a key rate limiting step in the bioavailability of topical ophthalmic formulations that incorporate poorly permeable drugs. Recent advances have greatly aided the ocular delivery of such drugs using colloidal drug delivery systems. Ribavirin, a poorly permeable BCS class-III drug, was incorporated in bioadhesive multiple W/O/W microemulsion (ME) to improve its corneal permeability. The drug-loaded ME was evaluated regarding its physical stability, droplet size, PDI, zeta potential, ultrastructure, viscosity, bioadhesion, in vitro release, transcorneal permeability, cytotoxicity, safety and ocular tolerance. Our ME possessed excellent physical stability, as it successfully passed several cycles of centrifugation and freeze–thaw tests. The formulation has a transparent appearance due to its tiny droplet size (10 nm). TEM confirmed ME droplet size and revealed its multilayered structure. In spite of the high aqueous solubility and the low permeability of ribavirin, this unique formulation was capable of sustaining its release for up to 24 h and improving its corneal permeability by 3-fold. The in vitro safety of our ME was proved by its high percentage cell viability, while its in vivo safety was confirmed by the absence of any sign of toxicity or irritation after either a single dose or 14 days of daily dosing. Our ME could serve as a vehicle for enhanced ocular delivery of drugs with different physicochemical properties, including those with low permeability.

中文翻译：

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使用生物粘附性多种微乳剂技术增强了通透性差的药物的角膜穿透力。

角膜渗透是掺入渗透性差的药物的局部眼科制剂生物利用度中的关键速率限制步骤。最近的进展极大地帮助了使用胶体药物递送系统眼部递送此类药物。利巴韦林是一种渗透性差的BCS III类药物，已掺入生物粘附性多种W / O / W微乳剂（ME）中以改善其角膜通透性。评价了载药的ME的物理稳定性，液滴大小，PDI，ζ电位，超微结构，粘度，生物粘附性，体外释放，角膜通透性，细胞毒性，安全性和眼耐受性。我们的ME具有出色的物理稳定性，因为它成功通过了多个离心和冻融测试循环。由于其微小的液滴尺寸（10 nm），该制剂具有透明的外观。TEM证实了ME液滴的大小，并揭示了其多层结构。尽管利巴韦林具有高水溶性和低渗透性，但这种独特的配方仍能够维持长达24小时的释放并将其角膜通透性提高3倍。我们的ME的体外安全性通过其高百分比的细胞生存力得到证明，而其体内安全性则通过单剂量或每天给药14天后没有任何毒性或刺激性迹象得到证实。我们的ME可以用作增强眼部输送具有不同理化特性（包括低渗透性）的药物的媒介。这种独特的配方能够维持长达24小时的释放并将其角膜通透性提高3倍。我们的ME的体外安全性通过其高百分比的细胞生存力得到证明，而其体内安全性则通过单剂量或每天给药14天后没有任何毒性或刺激性迹象得到证实。我们的ME可以用作增强眼部输送具有不同理化特性（包括低渗透性）的药物的媒介。这种独特的配方能够维持长达24小时的释放并将其角膜通透性提高3倍。我们的ME的体外安全性通过其高百分比的细胞生存力得到证明，而其体内安全性则通过单剂量或每天给药14天后没有任何毒性或刺激性迹象得到证实。我们的ME可以用作增强眼部输送具有不同理化特性（包括低渗透性）的药物的媒介。