Abstract
Purpose :
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 poly lactic glycolic acid (PLGA) capsule for dosage-controllable drug delivery implants to avoid the burst release and control the dose only when needed.
Methods :
We have developed a biodegradable PLGA implant enclosing light-activated liposomal drug (methotrexate). The PLGA implant has nano-sized pores where methotrexate (MTX) was released through when 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 irradiated near infrared laser (NIR, 1064 nm) through the lens of rabbit eyes to release MTX and fluorescence dye for visualization. The MTX release by laser was quantified based on in vivo imaging.
Results :
We created a pore size less than 5 nm to selectively release drug molecules only upon laser irradiation leaving the liposomal drug inside the capsule (p<0.05). We observed the nanopore size increased during degradation over 6 months in physiological conditions via scanning electron microscopy.
Shrinkage of the implant structure, observed on Day 180, was attributed to the degradation process. No adverse event due to the implant was observed on the retina via fundus, ultrasound exam and histology, during the 6 months. The implant did not seem to interfere with vision of the rabbits, based on their behavior. The location and position of the implant was not significantly changed.
Lastly, the dose released in vivo by laser followed the first-order kinetics and daily/weekly dose was clinically relevant (~50 ug per week).
Conclusions :
We successfully showed effective drug release from a nanoporous PLGA implant using pulsed NIR laser irradiation both in vitro and in vivo. The drug delivery system was safe and stable against leakage for 6 months. The light-activated drug delivery system that we developed will provide tightly-controlled release without burst release. Thus, the drug delivery system could be potentially used for long-term posterior eye disease treatment.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.