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无防腐剂曲安奈德丙酮混悬液与“传统”曲安奈德制剂的比较:颗粒大小对视网膜生物相容性的影响。

Preservative-free triamcinolone acetonide injectable suspension versus "traditional" triamcinolone preparations: impact of aggregate size on retinal biocompatibility.

机构信息

Department of Ophthalmology, Tübingen University Eye Hospital, University of Tübingen, Tübingen, Germany.

出版信息

Retina. 2011 Nov;31(10):2050-7. doi: 10.1097/IAE.0b013e318214d076.

DOI:10.1097/IAE.0b013e318214d076
PMID:21747324
Abstract

PURPOSE

To evaluate the biocompatibility of the three currently most commonly used triamcinolone acetonide (TA) preparations on retinal cells.

METHODS

Preservative containing KL (Kenalog-40; Bristol-Myers Squibb, Princeton, NJ), compounded preservative-free triamcinolone acetonide (PFTA; compounded from Volon A; Dermapharm, Vienna, Austria), and preservative-free triamcinolone acetonide injectable suspension (TRIESENCE; Alcon, Inc, Fort Worth, TX) (0.01-1 mg/mL) were either added directly on top or separated by a Boyden chamber filter or by a layer of vitreous to confluent cell cultures of retinal pigment epithelial cells (ARPE19) or retinal ganglion cells (RGC5). The distribution pattern of the TA crystals was assessed microscopically. Cell viability was assessed using MTT-ELISA and Live/Dead-Assay.

RESULTS

Sedimentation of triamcinolone acetonide injectable suspension, KL, or PFTA caused a pronounced decrease in cell viability. Cytotoxicity was most pronounced when triamcinolone acetonide injectable suspension and PFTA were used. Without direct sedimentation of TA crystals on top of the cells, none of the three formulations were cytotoxic. Triamcinolone acetonide injectable suspension showed the largest and most dense TA crystal aggregates on top of the cells.

CONCLUSION

Retinal cytotoxicity of TA seems only to occur when there is intimate contact of TA crystals with the cellular membrane. Cytotoxicity depends on the number and size of TA crystal aggregates-with larger conglomerates being more harmful. Of the TA formulations tested, triamcinolone acetonide injectable suspension had the strongest tendency to form large TA crystal conglomerates and to gravitate downward.

摘要

目的

评估目前最常用的三种曲安奈德(TA)制剂在视网膜细胞上的生物相容性。

方法

含有防腐剂的 KL(肯罗格-40;百时美施贵宝,普林斯顿,新泽西州)、无防腐剂的复方曲安奈德丙酮(PFTA;从 Volon A 配制;Dermapharm,维也纳,奥地利)和无防腐剂的曲安奈德丙酮混悬注射液(TRIESENCE;爱尔康公司,沃思堡,德克萨斯州)(0.01-1mg/mL)直接添加到汇合的视网膜色素上皮细胞(ARPE19)或视网膜神经节细胞(RGC5)的细胞培养物顶部,或者通过 Boyden 室过滤器或玻璃体液层隔开。用显微镜评估 TA 晶体的分布模式。用 MTT-ELISA 和 Live/Dead 测定法评估细胞活力。

结果

曲安奈德丙酮混悬注射液、KL 或 PFTA 的沉淀导致细胞活力明显下降。当使用曲安奈德丙酮混悬注射液和 PFTA 时,细胞毒性最为明显。当 TA 晶体没有直接沉淀在细胞顶部时,三种制剂均无细胞毒性。曲安奈德丙酮混悬注射液在细胞顶部显示出最大和最密集的 TA 晶体聚集体。

结论

只有当 TA 晶体与细胞膜密切接触时,TA 才会对视网膜产生细胞毒性。细胞毒性取决于 TA 晶体聚集体的数量和大小-较大的聚集体更有害。在所测试的 TA 制剂中,曲安奈德丙酮混悬注射液具有形成大 TA 晶体聚集体和向下移动的最强趋势。

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