Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Institute of Biophysics, Biological Research Centre,, Szeged, Hungary.
Drug Des Devel Ther. 2021 Feb 3;15:351-360. doi: 10.2147/DDDT.S264745. eCollection 2021.
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.
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.
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.
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.
眼用制剂需要具有最佳的经角膜渗透能力，而这受到眼部复杂结构和防御机制的限制。局部眼用制剂的抗菌稳定性尤其重要。根据以往的研究，最常用的防腐剂苯扎氯铵会对角膜上皮细胞产生刺激性和毒性；因此，需要使用新型无毒、抗菌的药物。本研究开发了含有泼尼松龙的眼用制剂，预期具有最佳渗透性，且无毒性或刺激性作用。
在人角膜上皮细胞系（HCE-T）和离体角膜模型上研究了含泼尼松龙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溶解。将含锌的粘膜黏附性生物聚合物用作替代防腐剂，将其毒性与苯扎氯铵进行比较。
结果表明，含苯扎氯铵的样品对 HCE-T 细胞有毒性。生物聚合物处理后不会造成细胞损伤。免疫组织化学检测证实了这一点。与混悬剂配方相比，含泼尼松龙-环糊精复合物的配方的体外渗透性显著提高。根据离体渗透研究，含生物聚合物的样品的渗透性显著降低。
考虑到目标配方的粘膜黏附特性，预期在给药后会有更长的吸收时间，需要的给药频率也会更低。可以说，这些制剂是具有创新性的方法，作为具有最佳药物渗透性的新型无毒眼科制剂。
