Faculty of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China; School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Int J Pharm. 2021 Mar 1;596:120226. doi: 10.1016/j.ijpharm.2021.120226. Epub 2021 Jan 21.
Ocular safety/biocompatibility is an essential element of ophthalmic drug delivery. We previously applied poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-b-PCL) micelles to deliver dasatinib for the management of proliferative vitreoretinopathy (PVR) in vitro. Herein, we seek to ascertain the ocular safety/compatibility of blank and dasatinib loaded PEG-b-PCL micelles, which will set the stage for the future in vivo efficacy evaluations and/or clinical translation for PVR or other eye diseases.
To access the safety of blank and dasatinib loaded micelles, in vitro cell based assays (LDH cell membrane damage test, SRB cytotoxicity, TEER and permeability of RPE tight junctions), in vivo slit lamp biomicroscopy and optical coherence tomography, Ex vivo histology (H&E staining, GFAP immunofluorescence staining and TUNEL assay) were undertaken.
Both blank and dasatinib loaded micelles showed remarkable safety profiles at cellular levels. They also caused negligible ocular toxicity/abnormalities up to 28 days post-intravitreal injection in mice. The micelles did not insult the cornea, as demonstrated by slit-lamp biomicroscopy. Ex vivo histology and in vivo optical coherence tomography revealed a normal retinal structure with minimal apoptosis and stresses.
Taken together, both blank and dasatinib loaded micelles appear to be safe and their applications in drug delivery for eye diseases should be explored.
眼部安全性/生物相容性是眼科药物输送的一个重要因素。我们之前应用聚乙二醇-嵌段-聚己内酯（PEG-b-PCL）胶束来输送达沙替尼，以用于体外增殖性玻璃体视网膜病变（PVR）的治疗。在此，我们旨在确定空白和载达沙替尼的 PEG-b-PCL 胶束的眼部安全性/相容性，这将为未来 PVR 或其他眼部疾病的体内疗效评估和/或临床转化奠定基础。
为了评估空白和载达沙替尼的胶束的安全性，我们进行了体外细胞水平的测定（LDH 细胞膜损伤试验、SRB 细胞毒性、TEER 和 RPE 紧密连接的通透性）、体内裂隙灯生物显微镜和光学相干断层扫描检查、以及体外组织学（H&E 染色、GFAP 免疫荧光染色和 TUNEL 检测）。
空白和载达沙替尼的胶束在细胞水平上均表现出显著的安全性。在小鼠玻璃体腔注射后 28 天内，它们也几乎没有引起眼部毒性/异常。通过裂隙灯生物显微镜检查，胶束未损伤角膜。组织学和体内光学相干断层扫描显示，视网膜结构正常，凋亡和应激最小。
综上所述，空白和载达沙替尼的胶束似乎都是安全的，它们在眼部疾病药物输送中的应用值得进一步探索。
