Abstract
Purpose :
Topical ocular drug delivery systems suffer from limitations to reach the retina, but approaches have been explored to overcome these limitations by addressing ocular residence time and applying controlled release strategies. We have developed a topical drug delivery platform incorporating a thermoresponsive gel and porous biocompatible metal-organic frameworks (MOFs). Herein, we hypothesize that our MOF-based topical drug delivery platform will show detectable levels of drug in the vitreous humor and retina to provide an alternative to intravitreal injections.
Methods :
Zeolitic imidazolate framework (ZIF-8) were synthesized in a purely aqueous solution of Zn2+ and 2-methylimidazole at a molar ratio of 1:16. PLGA microparticles (MPs) were synthesized using a double emulsion solvent-evaporation protocol. Ovalbumin was loaded into the particles at a mass of 10-40mg and incorporated into a thermoresponsive gel. Biodistribution studies involved healthy New Zealand white rabbits (n=5) - the right eye was given a 100µL of gel with particles, or a 50µL injection of 10 mg/mL ovalbumin solution. The left eye was the experimental control. At 1, 3, 7, and 14 days, rabbits were sacrificed, and both eyes were removed. Aqueous humor, vitreous humor, retina-choroid and plasma were collected, and time-dependent concentrations were quantified with ELISA.
Results :
After one administration of the topical delivery system, ovalbumin is detectable in the aqueous humor, vitreous humor, retina-choroid, and plasma. Interestingly, ovalbumin concentrations in the retina-choroid are 9x the concentration in the vitreous humor (~1 ng/mL). However, these concentrations are 105 lower than what is seen with intravitreal injections after 3 days.
Conclusions :
Topical ocular drug delivery systems that increase ocular surface residence times and incorporate controlled release strategies have the potential to provide retinal disease patients with an alternative to intravitreal injections. Our results suggest that our topical delivery platform can increase the ocular surface residence time and control the release of ovalbumin. Although high concentrations of ovalbumin are detectable in the retina-choroid, these levels are below the therapeutic levels of anti-VEGF medication; however, continuous presentation of drug makes these comparisons difficult to interpret and modifications can be further explored.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.