Background: Optimal transcorneal penetration is necessary for ocular therapy; meanwhile, it is limited by the complex structure and defensive mechanisms of the eye. Antimicrobial stability of topical ophthalmic formulations is especially important. According to previous studies, the mostly used preservative, benzalkonium-chloride is irritative and toxic on corneal epithelial cells; therefore, novel non-toxic, antimicrobial agents are required. In this study, prednisolone-containing ophthalmic formulations were developed with expected optimal permeation without toxic or irritative effects.
Methods: The toxicity and permeability of prednisolone-containing eye drops were studied on a human corneal epithelial cell line (HCE-T) and ex vivo cornea model. The lipophilic drug is dissolved by the formation of cyclodextrin inclusion complex. Zinc-containing mucoadhesive biopolymer was applied as an alternative preservative agent, whose toxicity was compared with benzalkonium-chloride.
Results: As the results show, benzalkonium-chloride-containing samples were toxic on HCE-T cells. The biopolymer caused no cell damage after the treatment. This was confirmed by immunohistochemistry assay. The in vitro permeability was significantly higher in formulations with prednisolone-cyclodextrin complex compared with suspension formulation. According to the ex vivo permeability study, the biopolymer-containing samples had significantly lower permeability.
Conclusion: Considering the mucoadhesive attribute of target formulations, prolonged absorption is expected after application with less frequent administration. It can be stated that the compositions are innovative approaches as novel non-toxic ophthalmic formulations with optimal drug permeability.



中文翻译：

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眼部给药的新方法：含环糊精的粘膜粘附滴眼剂制剂的体外和离体研究

背景：最佳的经角膜穿透是眼部治疗所必需的。同时，它受到眼睛复杂的结构和防御机制的限制。局部眼用制剂的抗菌稳定性尤为重要。根据以往的研究，最常用的防腐剂苯扎氯铵对角膜上皮细胞具有刺激性和毒性；因此，需要新的无毒抗微生物剂。在这项研究中，开发了含有泼尼松龙的眼科制剂，具有预期的最佳渗透性，没有毒性或刺激作用。
方法：在人角膜上皮细胞系 (HCE-T) 和离体角膜模型上研究了含有泼尼松龙的滴眼液的毒性和渗透性。亲脂性药物通过形成环糊精包合物而溶解。含锌粘膜粘附生物聚合物被用作替代防腐剂，其毒性与苯扎氯铵进行了比较。
结果：结果表明，含有苯扎氯铵的样品对 HCE-T 细胞有毒。生物聚合物在处理后没有造成细胞损伤。这通过免疫组织化学测定得到证实。与混悬剂相比，具有泼尼松龙-环糊精复合物的制剂的体外渗透性显着更高。根据离体渗透性研究，含有生物聚合物的样品的渗透性显着降低。
结论：考虑到目标制剂的粘膜粘附特性​​，预期在应用后吸收时间延长且给药频率较低。可以说，这些组合物是具有最佳药物渗透性的新型无毒眼科制剂的创新方法。