Thiolated gellan gum/polyethylene glycol diacrylate hydrogels containing timolol maleate-loaded chitosan nanoparticles for ophthalmic delivery

The combination of hydrogels with nanoformulations can significantly enhance the delivery and effectiveness of drugs in ophthalmic drug delivery systems. In the current study, the polyethylene glycol diacrylate (PEGDA)/thiolated gellan gum (GGSH) hydrogels based on GGSH and PEGDA were prepared via thiol-ene reaction using Irgacure 2959 as a photoinitiator. To this end, the modification of GG was achieved by esterification of the hydroxyl groups of GG with the carboxyl group of mercaptopropionic acid with a free thiol amount of 95.5 μmol g^-1. To provide sustained release, chitosan nanoparticles (CSNPs) containing timolol maleate (TM) with 56.4% entrapment efficiency were synthesized by the desolvation method and encapsulated in the developed hydrogel. The values of zeta potential and particle size of CSNPs were +26.0 mV and 182.4 nm, respectively. The physico/chemical properties of the hydrogels were investigated via texture analyzer, FT-IR, XRD, and SEM. The<i>in vitro</i>degradation, swelling behavior, rheological assessments, cell viability testing, and porosity determination were evaluated. With the increase in PEGDA concentration, the mechanical properties were increased. While the rate of swelling, degradation, and drug release were decreased. The<i>in vitro</i>biocompatibility of hydrogels was confirmed using the MTT test. According to an<i>ex vivo</i>study, ocular drug delivery using the obtained transparent hydrogels is promising due to improved drug permeation and sustained release of TM via CSNPs.