Department of Chemical & Environment Engineering, College of Engineering and Applied Science, University of Cincinnati, 2901 Woodside Drive, Cincinnati, Ohio 45221, United States.
Department of Ophthalmology, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, Ohio 45267, United States.
ACS Appl Bio Mater. 2021 Feb 15;4(2):1461-1469. doi: 10.1021/acsabm.0c01334. Epub 2021 Jan 22.
To treat chronic posterior eye diseases, frequent intravitreal injections or sustained-release drug implants are the current standard of care. Sustained-release drug implants often involve burst release of the drugs and the dosage from the implants cannot be controlled after implantation, which may lead to local side effects. The present study attempts to develop a dosage-controllable drug delivery implant that consists of a nanoporous biodegradable PLGA capsule and light-activated liposomes. Controllable drug release from the implant was achieved using a pulsed near-infrared (NIR) laser both in vitro and in vivo. The in vitro drug release kinetics from two different initial dose implants, 1000 and 500 μg, was analyzed by fitting zero-order and first-order kinetics, as well as the Korsmeyer-Peppas and Higuchi models. The 1000 and 500 μg implants fit the first-order and zero-order kinetics model, respectively, the best. The multiple drug releases in the vitreous were determined by an in vivo fluorimeter, which was consistent with the in vitro data. The dose released was also clinically relevant. Histology and optical and ultrasound imaging data showed no abnormality in the eyes received implant treatment, suggesting that the drug delivery system was safe to the retina. This on-demand dose-controllable drug delivery system could be potentially used for long-term posterior eye disease treatment to avoid frequent invasive injections.
为了治疗慢性眼底疾病，目前的标准治疗方法是频繁进行玻璃体内注射或使用缓释药物植入物。然而，缓释药物植入物通常会导致药物的爆发释放，并且在植入后无法控制植入物中的药物剂量，这可能会导致局部副作用。本研究试图开发一种可控制药物释放的植入物，该植入物由纳米多孔可生物降解的 PLGA 胶囊和光激活脂质体组成。通过使用脉冲近红外（NIR）激光，在体外和体内均实现了对植入物的可控药物释放。通过拟合零级和一级动力学、Korsmeyer-Peppas 和 Higuchi 模型，分析了两种不同初始剂量（1000 和 500 μg）植入物的体外药物释放动力学。结果表明，1000 和 500 μg 植入物分别最佳拟合一级和零级动力学模型。通过体内荧光计确定玻璃体内的多次药物释放，与体外数据一致。释放的剂量也具有临床相关性。组织学、光学和超声成像数据显示，接受植入物治疗的眼睛没有异常，表明该药物输送系统对视网膜是安全的。这种按需剂量可控的药物输送系统可用于长期眼底疾病的治疗，以避免频繁的侵入性注射。
