用于增生性玻璃体视网膜病变的硅油包裹卡氮芥：I. 溶解度、稳定性（体外和体内）及抗增殖作用（体外）研究

BCNU in silicone oil in proliferative vitreoretinopathy: I. Solubility, stability (in vitro and in vivo), and antiproliferative (in vitro) studies.

作者信息

Chung H, Tolentino F I, Cajita V N, Ueno N, Refojo M F

机构信息

Eye Research Institute of Retina Foundation, Boston, MA 02114.

出版信息

Curr Eye Res. 1988 Dec;7(12):1199-206. doi: 10.3109/02713688809033224.

DOI:10.3109/02713688809033224

PMID:3229131

Abstract

Various pharmacologic agents have been tried to control proliferative vitreoretinopathy (PVR). However, most are water soluble and cannot be used with silicone oil (SO), a tamponade agent also used in PVR management. We evaluated a lipophilic, antiproliferative drug, BCNU, in regard to its solubility and stability in SO, its release from SO into an aqueous solution, and its effect on cell cultures. BCNU is soluble in SO (peak concentration in micrograms/ml 1020, 750, and 294 at 37 degrees C, 21 degrees C, and 4 degrees C, respectively), and stable (half-life = 6.7 weeks at 37 degrees C, 17.9 weeks at 21 degrees C). At 4 degrees C, no significant decrease in concentration up to eight weeks was noted. BCNU is released from SO to water (partition coefficient = 10.28 +/- 2.16). Its median inhibitory doses (ID50) on bovine retinal pigment epithelial (RPE), rabbit RPE, and subconjunctival fibroblast cells are 13, 1.9, and 15.6 micrograms/ml, respectively. BCNU may be a useful pharmacologic tool to control PVR.

摘要

人们已尝试使用各种药物来控制增殖性玻璃体视网膜病变（PVR）。然而，大多数药物是水溶性的，不能与硅油（SO）一起使用，硅油是一种也用于治疗PVR的填塞剂。我们评估了一种亲脂性抗增殖药物卡莫司汀（BCNU）在硅油中的溶解性和稳定性、其从硅油释放到水溶液中的情况以及对细胞培养的影响。卡莫司汀可溶于硅油（在37℃、21℃和4℃时的峰值浓度分别为1020、750和294微克/毫升），且具有稳定性（在37℃时半衰期为6.7周，在21℃时为17.9周）。在4℃时，长达八周的时间内未观察到浓度有显著下降。卡莫司汀从硅油释放到水中（分配系数 = 10.28 ± 2.16）。它对牛视网膜色素上皮（RPE）细胞、兔RPE细胞和结膜下成纤维细胞的半数抑制剂量（ID50）分别为13、1.9和15.6微克/毫升。卡莫司汀可能是控制PVR的一种有用的药物工具。