(663g) Dose-Controllable Long-Term Drug Delivery Implant

Repetitive intravitreal injections of drug or intravitreal injections of sustained-release corticosteroid implants (Ozurdex, Retisert, and Iluvien) are the current standard of care for the chronic diseases. However, these methods involve complications due to the high initial dose at the time of injection, known as burst release.
In this study, we have developed a size-exclusive nanoporous biodegradable polymer capsule for dosage-controllable drug delivery implants to avoid the burst release and control the dose only when needed. Light-activated liposomal drug (methotrexate) was enclosed in the polymer capsule. Methotrexate (MTX) was released through the capsule membrane when the implant was activated by laser, leaving the liposomal drug in the capsule. We have optimized the porosity and the pore size for MTX release kinetics, and tested the stability and the safety for 6 months in vivo rabbit eyes. We also demonstrated MTX release in vivo by irradiating near infrared laser (NIR, 1064 nm) through the lens of rabbit eyes. Lastly, we also demonstrated biodegradable sustained-release monoclonal antibody implant, which releases monoclonal antibodies slowly for 8 months to date. The technology allows us to avoid monthly invasive injections, which is the current standard of care for most chronic diseases that require antibodies as therapeutics. The drug delivery system that we developed is a platform technology which can be applied to different and/or multiple drugs. More importantly, the dose-controllability can avoid any side effects associated with high dose or uncontrollable dose.