Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
Biomaterials. 2019 Oct;217:119285. doi: 10.1016/j.biomaterials.2019.119285. Epub 2019 Jun 21.
Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug's residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits.
眼内注射和植入物用于将药物递送到视网膜,因为这些药物的治疗水平不能通过局部给药(即眼药水)来提供。为了到达视网膜,局部应用的药物会遇到泪液稀释、反射性眨眼和快速的液体引流,这些共同减少了药物在眼表面的停留时间。角膜位于泪液之下,是许多局部眼科药物进入眼睛的主要途径。我们假设,停留在角膜上的药物洗脱隐形眼镜将非常适合向眼睛(包括视网膜)递送药物。我们开发了一种基于隐形眼镜的地塞米松递送系统(Dex-DS),该系统可实现治疗水平的持续药物递送到视网膜。Dex-DS 由包裹在隐形眼镜内的地塞米松聚合物膜组成。佩戴 Dex-DS 的兔子实现了比密集(每小时)地塞米松滴注高 200 倍的视网膜药物浓度。相反,Dex-DS 显示出较低的系统(血清)地塞米松浓度。在兔子的一项疗效研究中,Dex-DS 成功抑制了由玻璃体内注射血管内皮生长因子(VEGF)引起的视网膜血管渗漏。在一项为期四周的健康兔子重复剂量生物相容性研究中,发现 Dex-DS 是安全的。