Preparation and evaluation of gellan gum-based hydrogels containing thiolated chitosan nanoparticles for efficient ocular delivery of timolol maleate

Abstract

Introduction: Long-term use of eye drops by glaucoma patients reduces patient compliance due to the low retention time of the drops on the eye surface. Therefore, designing a formulation of these drugs that can stay on the eye for an extended period of time and release the drug slowly, solves this problem.Aim: The purpose of this study is to design a thiolated chitosan nanoparticle formulation dispersed in gellan gam that can release Timolol Maleate with a minimum level of toxicity and in a way that is efficient for treating glaucoma.Methods: Thiol groups were added to chitosan. FT-IR and ellman’s method were used for qualitative and quantitative confirmation. We prepared the drug-loaded nanoparticles by desolvation method and the particle size, zeta potential and drug entrapment efficacy were determined. The rheological properties of the formulation were evaluated by a rheometer and drug release determined by using an immersed dialysis bag. The morphology of the formulation was studied using a scanning electron microscope (SEM). Cytotoxicity was evaluated by MTT method.Results: The FT-IR spectrum of the samples confirms the thiolation reaction. The amount of thiolation groups is 198.6 ± 18.7 micromole of thiol per gram of chitosan. The synthesized thiolated chitosan nanoparticles showed a particle size of 200 nm. The drug entrapment efficacy was 60.7%. Rheological studies showed that the addition of nanoparticles to the hydrogel has poor effect on the rheological properties. Drug release from nanoparticles in hydrogel is slower than traditional formulations. The morphology of the formulation has provided the enough space for the nanoparticles movement. Cytotoxicity test showed that there is no significant difference between the formulation and the control group.Conclusion: Based on our studies, TCNPs are a suitable option for long-term use of Timolol Maleate.