Alami-Milani Mitra, Zakeri-Milani Parvin, Valizadeh Hadi, Fathi Marzieh, Salatin Sara, Salehi Roya, Jelvehgari Mitra
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Pharm Dev Technol. 2020 Jul;25(6):704-719. doi: 10.1080/10837450.2020.1733606. Epub 2020 Mar 8.
The aim of the present research was to investigate the feasibility of developing polylactide-polycaprolactone-polyethylene glycol-polycaprolactone-polylactide (PLA-PCL-PEG-PCL-PLA) based micelles to improve ocular permeability of dexamethasone (DEX). PLA-PCL-PEG-PCL-PLA copolymers were synthesized by a ringopening polymerization method. DEX was loaded into the developed copolymers. The DEX-loaded micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS) methods. Cytotoxicity of the micelles obtained was investigated on L929 cell line. Cellular uptake was followed by fluorescence microscopy and flow cytometry analyses. The release behavior of DEX from the micelles as well as the drug release kinetics was studied. Corneal permeability was also evaluated using an bovine model. The pentablock copolymers were successfully synthesized. The TEM results verified the formation of spherical micelles, the sizes of which was approximately 65 nm. The micelles exhibited suitable compatibility on L929 cells. The release profile showed an initial burst release phase followed by a sustained release phase, the kinetic of which was close to the Weibull's distribution model. The micelles showed higher corneal permeability in comparison to a marketed DEX eye drop. Taken together, the results indicated that the PLA-PCL-PEG-PCL-PLA micelles could be appropriate candidates for the ocular delivery of DEX, and probably other hydrophobic drugs.
本研究的目的是探究开发基于聚丙交酯-聚己内酯-聚乙二醇-聚己内酯-聚丙交酯（PLA-PCL-PEG-PCL-PLA）的胶束以提高地塞米松（DEX）眼部通透性的可行性。通过开环聚合法合成了PLA-PCL-PEG-PCL-PLA共聚物。将DEX负载到所制备的共聚物中。使用透射电子显微镜（TEM）和动态光散射（DLS）方法对负载DEX的胶束进行表征。在所获得的胶束对L929细胞系上研究其细胞毒性。通过荧光显微镜和流式细胞术分析追踪细胞摄取情况。研究了DEX从胶束中的释放行为以及药物释放动力学。还使用牛模型评估了角膜通透性。成功合成了五嵌段共聚物。TEM结果证实形成了球形胶束，其尺寸约为65 nm。胶束在L929细胞上表现出合适的相容性。释放曲线显示出初始的突释阶段，随后是持续释放阶段，其动力学接近威布尔分布模型。与市售的DEX滴眼液相比，胶束显示出更高的角膜通透性。综上所述，结果表明PLA-PCL-PEG-PCL-PLA胶束可能是DEX以及可能其他疏水性药物眼部给药的合适候选物。
