Laser-Activated Drug Implant for Controlled Release to the Posterior Segment of the Eye

• Published in: ACS applied bio materials Vol. 4; no. 2; pp. 1461 - 1469
• Main Authors: He, Xingyu, Yuan, Zheng, Gaeke, Samantha, Kao, Winston W.-Y, Li, S. Kevin, Miller, Daniel, Williams, Basil, Park, Yoonjee C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15.02.2021
• Subjects: Animals; Carbocyanines; Drug Implants; Drug Liberation; Fluorescent Dyes; Lasers; Methotrexate - administration & dosage; Methotrexate - pharmacokinetics; Rabbits; triggered drug release; multiple releases; posterior eye diseases; long-term drug delivery; drug delivery; laser-triggered drug delivery; dose-controllable implant
• DOI: 10.1021/acsabm.0c01334
• ISSN: 2576-6422

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.