Mucoadhesive and responsive nanogels as carriers for sustainable delivery of timolol for glaucoma therapy

Topical administration to the eye for the treatment of glaucoma is a convenient route because it increases the patient comfort. Timolol can efficiently diminish the intraocular pressure (IOP) of the eye; however the topical application as a solution of timolol maleate (TM) has poor therapeutic index and presents severe side effects. The encapsulation of timolol in nanomaterials has appeared as a technology to increase its residence time in the eye thus achieving a sustained release and consequently diminishing the doses of this drug and their number. The preparation of nanogels (NGs) based on N-isopropylacrylamide (NIPA) and acrylic acid (AAc), easily synthesized by precipitation/dispersion free radical polymerization, is reported in this paper. Such NGs presented excellent dispersability in eye simulated fluid and ideal size for topical application. NGs can load efficiently timolol through ionic interaction, and the in vitro release showed that NGs deliver timolol in a sustained manner. In vivo sustained efficacy of the NGs-timolol nanoformulations was demonstrated in rabbit's glaucoma model, in which the IOP could be diminished and maintained constant for 48 h with only one application. Overall, the synthesized NGs in combination with timolol have potential as drug delivery system for glaucoma therapy.