In vitro and in vivo evaluation of rectal delivery of novel sulfasalazine-loaded hydrogels and nanofibers for enhanced ulcerative colitis therapy

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that mainly affects the colon and causes symptoms such as hematochezia, rectal urgency, tenesmus, and abdominal pain. UC has a multifactorial path ogenesis, characterized by a complex interplay of genetic predisposition, environmental factors, and alteration in the gut microbiota. Traditional oral therapy, such as sulfasalazine (SSZ), is usually associated with systemic side effects and poor bioavailability. In response, the current study formulated and compared two rectally adminis tered drug delivery systems, SSZ-loaded hydrogel (SSZIH) and SSZ-loaded nanofiber (SSZNF). Comprehensive characterization using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) demonstrated the integrity of composition, stability at body temperature, and the successful incorporation of all formulation ingredients into the drug delivery systems. Biocompatibility was also evaluated using an in vitro cytotoxicity assay. Moreover, in vivo test findings, assessed in a chemically induced colitis rat model showed that these formulations dramatically lowered oxidative stress indicators including malondialdehyde (MDA) and myeloperoxidase (MPO), and enhanced antioxidant enzyme activities glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)). These results suggest that SSZ delivery through a hydrogel and nanofiber system by the rectal pathway can be a more efficient and safer treatment for UC.