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Abstract

A microporous hydrogel was developed using sodium alginate (alg) and 4-aminosalicylic acid (4-ASA). The synthesized hydrogel was characterized using various analytical techniques such as Fourier transform infrared spectroscopy (FTIR), Carbon-13 nuclear magnetic resonance (13C-NMR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Additonal carboxyl and hydroxyl functional groups of 4-ASA provided significant lubrication and stress-triggered sol-gel transition to the conjugated hydrogel. In addition, cytotoxicity analysis was undertaken on the conjugated hydrogel using human dermal fibroblast-adult (HDFa) cells, displaying non-toxic characteristics. Drug release profiles displaying 49.6% in the first 8 h and 97.5% within 72 h, similar to the native polymer (42.8% in first 8 h and 90.1% within 72 h). Under applied external stimuli, the modified hydrogel displayed significant gelling properties and structure deformation/recovery behaviour, confirmed using rheological evaluation (viscosity and thixotropic area of 8095.3 mPas and 26.23%, respectively). The modified hydrogel, thus, offers great possibility for designing smart synovial fluids as a biomimetic aqueous lubricant for joint-related injuries and arthritis-induced conditions. In addtion, the combination of thixotropy, non-toxicity, and drug release capabilities enables potential viscosupplementation for clinical application.

1. Introduction

In the current study, we developed a novel microporous hydrogel based on sodium alginate and 4-ASA via carbodiimide coupling chemistry. This is the first report on the synthesis of an alginate-4-aminosalicylic acid based amide conjugate to the best of our knowledge. Furthermore, the modified hydrogel was found to be nontoxic and possesed drug release profiles simmilar to sodium alginate. Gelling ability and gel structure deformation/recovery behaviour was confirmed using rheological studies to evaluate the hydrogel as a stress-triggered hydrogel system. Development and evaluation of biopolymer-based soft hydrogel systems provide great possibilities for designing smart synovial fluids and may act as a biomimetic aqueous lubricant for arthritis treatment. Moreover, the combination of thixotropy, nontoxicity and drug release capabilities of the hydrogel enables significant potential for clinical application such as viscosupplementation in arthritis intervention.