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In this work, we developed a mildly cross-linked dendrimer hydrogel (mcDH) via aza -Michael addition of polyamidoamine (PAMAM) dendrimer G5 and polyethylene glycol diacrylate (PEG-DA, M n =575 g/mol). We chose the antiglaucoma drug brimonidine tartrate as a model drug and developed a new antiglaucoma drug formulation on the basis of mcDH. Cytotoxicity of the mcDH formulation to NIH3T3 fibroblasts, in vitro drug release kinetics and ex vivo drug permeability across the rabbit cornea were examined. We also studied interactions between PAMAM dendrimer and the drug using 1 H NMR spectroscopy for a mechanistic understanding of brimonidine release from the mcDH. mcDH was found to be efficient unionizing brimonidine tartrate to form and encapsulate brimonidine free base for sustained release and enhanced corneal permeation.

Mildly Cross-Linked Dendrimer Hydrogel Prepared via Aza-Michael Addition Reaction for Topical Brimonidine Delivery