Huang Xuetao, Liu Shaogang, Yang Yezhen, Duan Yiqin, Lin Ding
a Department of Ophthalmology, Changsha Aier Hospital , Changsha , China.
b Aier School of Ophthalmology, Central South University , Changsha , China , and.
Drug Deliv. 2017 Nov;24(1):452-458. doi: 10.1080/10717544.2016.1264498.
Corticosteroids have been used for treatment of posterior segment eye diseases, but the delivery of drug to the posterior segments is still a problem to resolve. In our study, we explore the feasibility of Sub-tenon's Controllable Continuous Drug Delivery to ocular posterior segment. Controllable continuous sub-tenon drug delivery (CCSDD) system, intravenous injections (IV) and sub-conjunctival injections (SC) were used to deliver dexamethasone disodium phosphate (DEXP) in rabbits, the dexamethasone concentration was measured in the ocular posterior segment tissue by Shimadzu LC-MS 2010 system at different time points in 24 h after first dose injection. Levels of dexamethasone were significantly higher at 12, 24 h in CCSDD than two other approaches, and at 3, 6 h in CCSDD than IV in vitreous body (p < 0.01); at 6, 12, 24 h in CCSDD than two other approaches, and at 1, 3 h in CCSDD than IV in retinal/choroidal compound (p < 0.01); at 3, 6, 12, 24 h in CCSDD than two other approaches, and at 1 h in CCSDD than IV in sclera (p < 0.05). The AUC in CCSDD group is higher than two other groups in all ocular posterior segment tissue. Our results demonstrated that dexamethasone concentration could be sustained moderately higher in the posterior segment by CCSDD than SC and IV, indicating that CCSDD might be a therapeutic alternative to treat a variety of intractable posterior segment diseases.
皮质类固醇已被用于治疗眼后段疾病,但将药物递送至眼后段仍是一个有待解决的问题。在我们的研究中,我们探讨了巩膜下可控持续药物递送至眼后段的可行性。采用可控持续巩膜下药物递送(CCSDD)系统、静脉注射(IV)和结膜下注射(SC)在兔体内递送地塞米松磷酸二钠(DEXP),在首次给药后24小时的不同时间点,通过岛津LC-MS 2010系统测量眼后段组织中的地塞米松浓度。CCSDD组在12、24小时时地塞米松水平显著高于其他两种给药方式,在玻璃体中,CCSDD组在3、6小时时地塞米松水平高于IV组(p < 0.01);在视网膜/脉络膜复合物中,CCSDD组在6、12、24小时时地塞米松水平高于其他两种给药方式,在1、3小时时CCSDD组高于IV组(p < 0.01);在巩膜中,CCSDD组在3、6、12、24小时时地塞米松水平高于其他两种给药方式,在1小时时CCSDD组高于IV组(p < 0.05)。CCSDD组在所有眼后段组织中的AUC均高于其他两组。我们的结果表明,CCSDD可使眼后段地塞米松浓度适度高于SC和IV组,这表明CCSDD可能是治疗各种难治性眼后段疾病的一种治疗选择。