Enhanced ocular delivery of timolol maleate through thiolated chitosan nanoparticles/gellan gum-based hydrogels.

In this study, a thiolated chitosan nanoparticles (TCS-NPs) formulation containing timolol maleate (TM) dispersed in gellan gum (GG) (TM@TCS-NPs/GG) was prepared for the ocular delivery of TM. To this end, thiol groups were added to chitosan (CS) which was confirmed by FT-IR, and Ellman's method with 198.6 ± 18.7 μmol/g sulfhydryl content. The drug-loaded NPs were prepared by the desolvation method, and the particle size, zeta potential, and drug entrapment efficacy were evaluated. The optimized TM-loaded TCS-NPs exhibited a particle size of 271.4 nm, a polydispersity index (PDI) of 0.3, and an entrapment efficiency of 60.3%. The rheological properties, morphology, and drug-release behavior of the formulations were studied. Rheological studies showed that adding NPs to the hydrogel has a negligible effect on the rheological properties. Drug release from NPs in the hydrogel is slower than free NPs formulations. Cytotoxicity test by MTT assay demonstrated no significant toxicity of the developed formulations. Based on the obtained results, the TCS-NPs/GG system demonstrates promising potential for sustained ocular drug delivery of TM.