Spitzer Martin S, Kaczmarek Radoslaw T, Yoeruek Efdal, Petermeier Katrin, Wong David, Heimann Hanno, Jaissle Gesine B, Bartz-Schmidt Karl U, Szurman Peter
Tübingen University Eye Hospital, University of Tübingen, Tübingen, Germany.
Invest Ophthalmol Vis Sci. 2009 May;50(5):2337-43. doi: 10.1167/iovs.08-2471. Epub 2008 Dec 20.
Triamcinolone acetonide (TA) has been proposed as an adjuvant to pars plana vitrectomy with silicone oil for the surgical treatment of proliferative vitreoretinopathy and proliferative diabetic retinopathy. However, to date no data about the distribution and pharmacokinetics of lipophilic TA injected into silicone oil have been reported.
An artificial vitreous space chamber was filled with silicone oil. TA was either injected or dispersed into silicone oil. TA release using a continuous flow model was measured spectrophotometrically. To determine the antiproliferative or cytotoxic effect of the released TA, monolayer cultures of retinal pigment epithelial cells (ARPE19) and retinal ganglion cells (RGC5) were used. Bromodeoxyuridine incorporation, MTT assay, and scanning electron microscopy were performed.
Injected TA sank slowly through the silicone oil and started to sediment below the silicone oil bubble shortly after injection. After the simulated intravitreal injection, no TA could be retrieved from the silicone oil bubble. In contrast, when a suspension of silicone oil and TA was prepared before injection, stable noncytotoxic amounts of TA (25 microg/mL) could be retrieved for up to 90 days. After mere injection (without previous suspension in silicone oil), the sedimented TA crystals showed a pronounced cytotoxic effect.
Intravitreally injected TA does not mix with silicone oil. TA crystals that sediment at the lower border of a silicone oil bubble may be harmful to retinal cells. A suspension of TA in silicone oil may exhibit safer extended release over several days.
已有人提出将曲安奈德（TA）作为辅助药物，与硅油一起用于玻璃体视网膜增殖性病变和增殖性糖尿病视网膜病变的玻璃体切割手术治疗。然而，迄今为止，尚无关于注入硅油中的亲脂性TA的分布和药代动力学的数据报道。
用人造玻璃体腔室填充硅油。将TA注入或分散于硅油中。采用分光光度法测定在连续流动模型下TA的释放情况。为确定释放出的TA的抗增殖或细胞毒性作用，使用了视网膜色素上皮细胞（ARPE19）和视网膜神经节细胞（RGC5）的单层培养物。进行了溴脱氧尿苷掺入试验、MTT试验和扫描电子显微镜检查。
注入的TA在硅油中缓慢下沉，注射后不久开始沉积在硅油泡下方。模拟玻璃体内注射后，无法从硅油泡中回收TA。相比之下，在注射前制备硅油和TA的混悬液时，在长达90天的时间内都能回收稳定的无细胞毒性量的TA（25微克/毫升）。单纯注射（未事先混悬于硅油中）后，沉积的TA晶体显示出明显的细胞毒性作用。
玻璃体内注射的TA不与硅油混合。沉积在硅油泡下缘的TA晶体可能对视网膜细胞有害。TA在硅油中的混悬液可能在数天内呈现更安全的缓释效果。
