*Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; and †Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan.
Cornea. 2014 May;33(5):521-6. doi: 10.1097/ICO.0000000000000086.
The aim of this study was to examine the ophthalmic additives responsible for modulating acute corneal epithelial toxicity induced by benzalkonium chloride (BAC) and investigate the ability of polyoxyethylene hydrogenated castor oil 40 (HCO-40) and polysorbate 80 (PS-80) to reduce the corneal toxicity and antimicrobial effects of BAC.
Cytotoxicity of the additives, which included glycerin, polyvinyl alcohol, propylene glycol, polyethylene glycol, and PS-80, on rabbit corneal epithelial cells was examined using the cell proliferation assay in the presence and absence of 0.02% BAC. The corneal transepithelial electrical resistance change after a 60-second exposure to HCO-40 or PS-80 mixed with 0.02% BAC was measured in living rabbits. Corneal damage was examined using scanning electron microscopy. The antimicrobial activities of HCO-40 and PS-80 with 0.02% BAC against Staphylococcus aureus, Propionibacterium acnes, Pseudomonas aeruginosa, Escherichia coli, and Streptococcus pneumoniae were assessed.
Of all the tested additives, only PS-80 could prevent the BAC-induced cytotoxicity. Corneal epithelial barrier function disorder caused by 0.02% BAC was significantly alleviated by either PS-80 or HCO-40 in a concentration-dependent manner. Scanning electron microscopy images showed an improvement of BAC-induced corneal epithelial toxicity after the addition of HCO-40 or PS-80. The antimicrobial effect of the BAC against P. aeruginosa, E. coli, and S. pneumoniae was reduced after adding HCO-40 or PS-80.
HCO-40 and PS-80 reduce acute corneal toxicity and the antimicrobial effect of BAC. Possible interactions between BAC and other additives should be taken into consideration when evaluating the toxicity and antibacterial properties of BAC.
本研究旨在探讨导致苯扎氯铵（BAC）诱导急性角膜上皮毒性的眼用添加剂，并研究聚氧乙烯氢化蓖麻油 40（HCO-40）和聚山梨酯 80（PS-80）降低 BAC 角膜毒性和抗菌作用的能力。
采用细胞增殖试验，在存在和不存在 0.02% BAC 的情况下，检测添加剂甘油、聚乙烯醇、丙二醇、聚乙二醇和 PS-80 对兔角膜上皮细胞的细胞毒性。在活兔中测量 60 秒暴露于 HCO-40 或 PS-80 与 0.02% BAC 混合物后角膜上皮跨上皮电阻的变化。使用扫描电子显微镜检查角膜损伤。评估 HCO-40 和 PS-80 与 0.02% BAC 对金黄色葡萄球菌、痤疮丙酸杆菌、铜绿假单胞菌、大肠杆菌和肺炎链球菌的抗菌活性。
在所测试的添加剂中，只有 PS-80 能够预防 BAC 诱导的细胞毒性。0.02% BAC 引起的角膜上皮屏障功能障碍通过 PS-80 或 HCO-40 以浓度依赖的方式得到显著缓解。扫描电子显微镜图像显示，添加 HCO-40 或 PS-80 后，BAC 诱导的角膜上皮毒性得到改善。添加 HCO-40 或 PS-80 后，BAC 对铜绿假单胞菌、大肠杆菌和肺炎链球菌的抗菌作用降低。
HCO-40 和 PS-80 降低 BAC 的急性角膜毒性和抗菌作用。在评估 BAC 的毒性和抗菌性能时，应考虑 BAC 与其他添加剂之间的可能相互作用。
