In vitro cytotoxicity of eight β-blockers in human corneal epithelial and retinal pigment epithelial cell lines: Comparison with epidermal keratinocytes and dermal fibroblasts

β-Blockers are a class of agents that have been used extensively in topical preparations for the treatment of glaucoma. Recent evidence indicates that they may also be useful in a number of retinal diseases. Because biocompatibility is of utmost importance in the treatment of ocular-related diseases, we compared the in vitro cytotoxicity, using the MTT assay, of eight clinically available β-blockers (propranolol, alprenolol, atenolol, labetalol, metoprolol, pindolol, timolol, and bisoprolol) on human corneal epithelial and retinal pigment epithelial cell lines. Primary and immortalized corneal and retinal cell lines were compared for their susceptibility to the cytotoxic effect of the drugs. The cytotoxicity of β-blockers was also evaluated on human skin keratinocytes and fibroblasts in order to investigate susceptibility differences as a function of the tissue of origin. Results demonstrated large differences in cytotoxicity (about 60-fold) for these closely related drugs on the same cell line. Conversely, only relatively small differences in cytotoxicity were observed between the different cell lines for the same drug, indicating that the mechanism of cytotoxicity is not cell-specific. Calculation of the ratio between the cytotoxicity of β-blockers and their β-blocking constant is presented as a potential tool to help identify the least irritating, most potent drug.     

松果菊苷固体脂质纳米粒的表征及体外细胞摄取评价

[目的]对本实验室前期处方优化的松果菊苷固体脂质纳米粒(ECH-SLN)的物理性质和体外细胞摄取情况进行评价,为今后眼部制剂的改进奠定基础。[方法]根据本实验室前期优化的处方,采用乳化-固化法制备ECHSLN,运用差示扫描量热法(DSC)及X射线衍射法(XRD)表征其物理性质,并选取人角膜上皮HCEpiC细胞与人晶状体上皮SRA 01/04细胞,对罗丹明123固体脂质纳米粒(Rhodamine 123-SLN,Rh 123-SLN)进行体外细胞毒性评价及细胞摄取研究。[结果] DSC结果显示仅松果菊苷和物理混合物(空白SLN∶松果菊苷=5∶1)在150℃出现松果菊苷的熔化吸热特征峰,空白SLN、ECH-SLN和物理混合物在110℃和230℃均出现SLN的两个熔化吸热特征峰;XRD结果显示松果菊苷和物理混合物在20°时出现明显的松果菊苷特征峰,空白SLN,ECH-SLN和物理混合物在20°～25°范围均显示SLN的范围特征峰;结果均表明松果菊苷作为药物以分子分散状态被包裹在固体脂质纳米粒(SLN)中;细胞活力影响实验结果显示Rh 123-SLN浓度为5.13μg/mL和10.25μg/mL时对两种细胞均无明显毒性,与对照组相比无显著性差异;细胞摄取实验结果表明Rh 123溶液不能被细胞所摄取,而Rh 123-SLN的细胞摄取量与药物浓度和孵育时间呈正相关。[结论] ECH-SLN能够将松果菊苷递送到眼细胞,这可能为氧化性白内障的治疗提供一种有效的药物递送系统。