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Yoonjee Park, Xingyu He, Zheng Yuan, Winston Kao; Long-term Dose-controllable Drug Delivery Implant. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2883.
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Repetitive intravitreal injections of drug or intravitreal injections of sustained-release corticosteroid implants 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.
Light-activated liposomal drug are enclosed in the capsule, and drug is released through the nanopores of the PLGA when activated by laser, leaving the liposomal drug in the capsule. This approach can prevent the drug-encapsulating particles from being cleared by containing the particles in a capsule-shaped implant.We have optimized the nanoporous structure by tuning the ratio between porogen (poly ethylene glycol) and utilizing high molecular weight PLGA for long term, 6 months, and tested the degradation, stability against passive leakage and the safety in vivo rabbit eyes.
We used 0.1 porogen ratio to create 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). Degradation of the implant seemed to occur between 4 and 5 months, but the intact cylindrical shape was observed up to 4 months. The in vivo degradation results were consistent with in vitro degradation data at 37 C in the PBS solution where the pore sizes of the PLGA capsule at month 6 were identical, suggesting the main degradation mechanism is chemical not biological.In vivo fluorescence imaging also verified that the implants contain a significant amount of the dye at the 4 month time point, indicating stability against passive leakage. No adverse event due to the implant was observed on the retina via fundus, ultrasound exam and histology. The results also indicate that the liposomal drug released by degradation did not cause any damage to the retina.
We have successfully developed size-exclusive nanoporous biodegradable implants that releases drug in an on-demand fashion for a long time. Degradation of the implant was observed in the vitreous with no adverse effect.
This is a 2020 ARVO Annual Meeting abstract.
Ultrasound images of the implant in vivo at Day 0 (A), Day 120 (B) and Day 180 (C). (D) shows the gross cut-open image of implant in a rabbit eye at Day 180.
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