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Abstract #126863 Published in IGR 25-2
Acetazolamide-loaded intravitreal implants for the treatment of glaucoma: formulation, physicochemical characterization and assessment of in vitro and in vivo safety
da Silva PHR; de Castro MA; Ribeiro MCS; Gonçalves LTA; de Melo LA; Freitas-Marques MB; Pedrosa TA; Pianetti GA; Fialho SL; Yoshida MI; da Nova Mussel W; Silva-Cunha A; Fernandes CInternational Journal of Pharmaceutics 2025; 674: 125507
Glaucoma is a leading cause of permanent blindness, currently affecting over 75 million individuals worldwide. Treatments primarily aim to lower intraocular pressure (IOP), with acetazolamide being a common pharmacotherapy. However, systemic side effects and poor bioavailability limit its clinical effectiveness. This study presents the development and physicochemical and safety evaluation of biodegradable intravitreal implants loaded with acetazolamide using polylactic-co-glycolic acid (PLGA), designed to enhance targeted drug delivery directly to the vitreous humor. The acetazolamide-loaded PLGA implants were successfully fabricated via hot molding, yielding cylindrical rods measuring 5.00 ± 0.02 mm in diameter. Incorporation efficiency reached approximately 92 %, with a uniform drug dose of 230 μg/g. Comprehensive physicochemical characterization confirmed compatibility between the drug and polymer, with stability demonstrated for at least 6 months. The implants exhibited a biphasic drug release profile, sustaining approximately 50 % of the drug over 42 days without an initial burst, indicating their potential for effective and prolonged glaucoma management. Safety assessments revealed that the implants did not induce retinal toxicity at doses up to 0.020 mmol/L. In vitro cytotoxicity assays with ARPE-19 cells and in vivo tests - electroretinography, Goldmann applanation tonometry, optical coherence tomography, and histological analysis - showed no adverse effects on retinal function or structure. Importantly, the implants significantly reduced IOP in normotensive rabbits, confirming their therapeutic potential. This innovative approach represents a promising alternative for glaucoma treatment, addressing the limitations of current modalities while providing sustained drug delivery and enhanced safety.
Pharmaceutical Products Department, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
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