Next-Generation Solid Dispersion of Andrographolide Attenuated Inflammation and Oxidative Stress in an Activated...

Ulcerative colitis (UC) is fundamentally mediated by macrophage-driven immune dysregulation that amplifies mucosal inflammation. Andrographolide (AGD) has potent anti-inflammatory and antioxidant properties; however, AGD shows poor water solubility and bioavailability. To surmount these challenges, next-generation solid dispersion of AGD with soluplus and TPGS was engineered via the solvent evaporation method. Optimized SD8 demonstrated a ~ 7.14-fold upsurge in solubility, 18.78 ± 0.98% drug content, 93.86 ± 3.19% assay, micellar colloid size of 220.5 ± 20.8 nm, and ζ-potential of -4.18 ± 0.03 mV in aqueous dispersion. ATR-FTIR and ¹H-NMR analyses indicated that the -OH group of AGD participated in intermolecular hydrogen bonding with soluplus and TPGS. Moreover, the halo diffraction pattern, the vanishing of the endothermic peak, the lack of birefringence under polarized light, and the loss of crystallinity collectively confirmed the amorphous nature of SD8. SD8 exhibited ~ 2.06-fold decline of contact angle, ~ 4.70- and ~ 2.94-fold boosts in dissolution rate in simulated intestinal fluid (SIF) and simulated colonic fluid (SCF), respectively, and ~ 40.7-fold upsurge in apparent permeability coefficient compared to AGD. SD8 markedly enhanced cytoprotection over AGD, evidenced by significantly lower IC₅₀ values in both lipopolysaccharide (LPS)-activated (7.17 ± 0.15-µg/mL; P < 0.0001) and H₂O₂-exposed (7.92 ± 0.15-µg/mL; P < 0.01) RAW264.7 macrophages. SD8 significantly suppressed LPS-induced NO production (P < 0.05) and pro-inflammatory mediators (IL-1β, IL-6, TNF-α; P < 0.0001). SD8 markedly reduced ROS levels, significantly restored antioxidant enzymes SOD (P < 0.0001), CAT (P < 0.001), GSH (P < 0.0001), and lowered TBARS (P < 0.0001) with respect to H₂O₂-exposed RAW264.7 cells. In conclusion, SD8 represents an auspicious drug delivery tactic for further preclinical evaluation to advance its translational potential in the therapeutic management of UC.