Gellan gum/gelatin Schiff-base hydrogel for ocular drug delivery of timolol maleate.

In ocular drug delivery, increasing the retention time of the drug by using in situ forming hydrogels can be effective. In the current study, hydrogels with suitable gelling properties were obtained using oxidized gellan gum as a green crosslinker and gelatin via Schiff-base linkages. In the first step, oxidation of gellan gum was done to obtain aldehyde groups, and in situ gelling hydrogels were formed based on a simplistic Schiff-base reaction between oxidized gellan gum and amine groups of gelatin in the presence of β-glycerophosphate disodium salt as a pH adjustment agent and gelation accelerator. The calculated aldehyde content was about 64.5% by the titration method. By optimizing the concentration of gelatin, oxidized gellan gum, and β-glycerophosphate disodium salt, hydrogels with a fast gelation time were obtained. The synthesized hydrogels were investigated via Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscope (SEM), X-ray diffraction (XRD), swelling degree, and rheological properties. The effect of oxidized gellan gum and gelatin concentration on the physical and chemical characteristics of the obtained hydrogel system were studied. The results of in vitro and ex vivo research indicated that the prepared hydrogel with a high concentration of oxidized gellan gum and gelatin had a higher release rate, stronger network, and homogeneous morphological structure. The synthesized hydrogels have adequate porosity for drug loading (around 98-99%). Also, the MTT cytotoxicity test on bone marrow mesenchymal stem cells (BMSCs) confirmed that the developed hydrogels with green crosslinker do not have cytotoxic effects. In vitro and ex vivo drug release tests demonstrated a facile preparation strategy for fast-gelling hydrogels that can be considered as an appropriate candidate for timolol maleate delivery in glaucoma treatment.