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Dexamethasone - PAMAM dendrimer conjugates for retinal delivery: preparation, characterization and in vivo evaluation
Burçin Yavuz1, Sibel Bozdağ Pehlivan1, Burcu Sümer Bolu2
1Pharmaceutical Technology Department, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Objective:
Ocular diseases affecting retina, such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma are the major causes of blindness, and their treatment is still a challenge due to the special structure of the eye. The purpose of this study was to prepare a sustained release DEX conjugate formulation with enhanced ocular permeation using poly(amidoamine) (PAMAM) dendrimers and to evaluate the effects of conjugation on DEX release and ocular residence time.
Methods:
PAMAM G3.5 and PAMAM G4.5 dendrimers were used to prepare DEX conjugates, and conjugation was confirmed using (1) H-NMR. Formulations were evaluated in terms of drug release in the presence of ocular enzymes and cytotoxicity on ARPE19 cell lines. Fluorotron analysis was performed and ocular pharmacokinetic properties of DEX-PAMAM conjugates were studied in Sprague Dawley rats following intravitreal and subconjunctival applications.
Key Findings:
The results indicated that DEX-PAMAM conjugates were able to enhance ocular permeability and ocular tissue levels of DEX following subconjunctival injection, and results were encouraging when compared to the literature that has reported DEX getting cleared from vitreous in 3 h.
Conclusion:
Current studies are focused on formulation improvement to enhance hydrolysis and clearance time.
