Cyclodextrins and topical drug delivery to the anterior and posterior segments of the eye
Cyclodextrins and topical drug delivery to the anterior and posterior segments of the eye
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DOI：
10.1016/j.ijpharm.2017.04.010
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发表时间：
2017-10-15
影响因子：
5.8
通讯作者：
Stefansson, Einar
中科院分区：
文献类型：
--
作者：
Loftsson, Thorsteinn;Stefansson, Einar
一般认为，在局部应用水性低粘度滴眼液后，几乎不可能在眼后段获得治疗药物浓度。因此，玻璃体内药物注射和药物植入目前用于治疗后段疾病，例如黄斑水肿。本文描述了如何通过对药物渗透屏障的适当分析和众所周知的药用赋形剂的应用，设计可将亲脂性药物递送至眼后段的水性滴眼剂，以及此类滴眼剂如何可在眼前段维持高药物浓度。通过逐步优化，设计了含有平均直径为2-4 μ m的固体药物/环糊精复合物微粒、溶解的药物/环糊精复合物纳米颗粒和溶解的药物分子在低粘度水性滴眼介质中的滴眼液。滴眼液给药后，微粒缓慢溶解并在水性泪液中保持接近饱和药物浓度数小时。使用多佐胺和地塞米松作为样品药物的家兔研究和人体临床评价表明，滴眼液可将大量药物递送至眼后段和眼前段。临床研究表明，该滴眼液可以取代目前用于治疗眼科疾病的玻璃体内注射和植入物，并减少给药频率，这两者都可以提高患者的依从性。(C)2017爱思唯尔B. V.保留所有权利。
It is generally believed that it is virtually impossible to obtain therapeutic drug concentrations in the posterior segment of the eye after topical application of aqueous, low viscosity eye drops. Thus, intravitreal drug injections and drug implants are currently used to treat diseases in the posterior segment such as macular edema. Here it is described how, through proper analysis of the drug permeation barriers and application of well-known pharmaceutical excipients, aqueous eye drops are designed that can deliver lipophilic drugs to the posterior segment as well as how such eye drops can maintain high drug concentrations in the anterior segment. Through stepwise optimization, eye drops containing solid drug/cyclodextrin complex microparticles with a mean diameter of 2-4 mu m, dissolved drug/cyclodextrin complex nanoparticles and dissolved drug molecules in an aqueous eye drop media of low viscosity were designed. After administration of the eye drops the microparticles slowly dissolved and maintained close to saturated drug concentrations in the aqueous tear fluid for several hours. Studies in rabbits and clinical evaluations in humans, using dorzolamide and dexamethasone as sample drugs, show that the eye drops deliver significant amounts of drugs to both the posterior segment and anterior segment of the eye. Clinical studies indicate that the eye drops can replace intravitreal injections and implants that are currently used to treat ophthalmic diseases and decrease frequency of drug administration, both of which can improve patient compliance. (C) 2017 Elsevier B.V. All rights reserved.