A pH-responsive, biocompatible, and non-toxic citric acid cross-linked polysaccharide-based hydrogel from Salvia spinosa L. offering zero-order drug release

Abstract

Salvia spinosa seeds hydrogel (SSH) was chemically cross-linked with four different concentrations of citric acid (CA), i.e., 1.25%, 2.5%, 5.0%, and 10.0%. The fabrication of CA cross-linked SSH (CA-cl-SSH) was confirmed through Fourier transform infrared spectroscopic analyses. The CA-cl-SSH appeared thermally as stable as SSH. The CA-cl-SSH was found pH-sensitive and exhibited maximum swelling in deionized water (DW) as compared to the buffers of pH 1.2, 6.8, and 7.4 following the order pH 1.2 < pH 6.8 < pH 7.4 < DW. Stimuli-responsive swelling and deswelling (on-off switching) behavior of CA-cl-SSH (2.5% CA) was found reversible at pH 7.4 and 1.2, in DW and normal saline, and DW and ethanol. CA-cl-SSH sustained the release of aceclofenac following the zero-order kinetics and non-Fickian diffusion mechanism. The in vivo radiographic images revealed the presence of CA-cl–SSH–based tablet formulation in GIT for 9 h. Hemocompatibility studies confirmed the non-thrombogenic and non-hemolytic potential of CA-cl-SSH. Acute oral toxicity study presented its safety profile owing to the absence of any mortality and toxic effects. Therefore, it can be concluded that CA-cl-SSH is a novel stimuli-responsive, biocompatible, and non-toxic polysaccharide-based biomaterial having the potential for the development of sustained-release drug delivery system following zero-order kinetics.