Innovative mucoadhesive silk sericin/xanthan gum/polystyrene sulphonate (TSP-XNTG-g-PSS) based composites for vaginal delivery featuring instant spermicidal activity.

Over the last few decades, unintended pregnancy has remained a major concern, as conventional contraceptives often cause irritation, reduced efficacy, and low adherence. The current research endeavour aimed to synthesize tasar silk protein/xanthan gum grafted polystyrene sulphonates (TSP-XNTG-g-PSS) based composite system, which would reveal an advantageous, non-toxic, mucoadhesive contraceptive for local vaginal delivery designed for potential prevention of unintended pregnancies. In this context, XNTG can be conjugated with TSP and PSS through a microwave-assisted free radical grafting reaction, utilising APS as the initiator. A central composite design based on response surface methodology was employed to optimize conjugates (F2), which showed the highest grafting (88.50 ± 1.0%) and intrinsic viscosity (14.38 dl/g). Further, these optimized conjugates were structurally characterized with FTIR, 1H NMR, 13C NMR, TGA, XRD, and FESEM analysis. Native XTNG, novel TSP, PSS, F1, F2, and F3 revealed variable zeta potentials (-6.71 mV to -21.5 mV), acceptable particle sizes (704-4257 d.nm), and PDI values (0.314-1.0), and favourable contact angle. Among various composites (F1-F3), F2 demonstrated excellent swelling profiles and mucoadhesion properties. These composites were hemocompatible and conferred anti-inflammatory and antioxidant activities. The ex vivo spermicidal studies confirm that F2 significantly reducing sperm motility and vitality, while enhancing morphological abnormalities. The composites exhibited remarkable cytocompatibility, as demonstrated by the MTT assay in HeLa cells, and showed no observable toxicity in zebrafish gill histopathological evaluations. Thus, the newly developed polymeric composites demonstrate potent spermicidal action with favourable safety, offering a promising intravaginal contraceptive platform for reducing the risk of unwanted pregnancy.