Spray drying-assisted development of hydroxypropyl methylcellulose acetate succinate microparticles for andrographolide delivery: an in-vivo study in experimental ulcerative colitis.

Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease distinguished by colonic inflammation and mucosal injury; therefore, targeted suppression of underlying inflammatory pathways represents a rational strategy for developing an effective drug delivery system. In the current investigation, Andrographolide (ADG) loaded pH-responsive hydroxypropyl methylcellulose acetate succinate-based microparticles (ADG-HPMC-AS MPs) were engineered by spray-drying technique and optimized using Box-Behnken Design to achieve desirable physicochemical and biopharmaceutical attributes. Optimized ADG-HPMC-AS MPs exhibited particle size 9.25 ± 0.89 µm, zeta potential (ζ) -0.80 ± 0.70 mV, drug loading 8.97 ± 0.49%, entrapment efficiency 53.81 ± 2.96%, and spherical shape. Next, a plethora of solid-state analyses validated effective ADG encapsulation, improved thermal stability, and amorphous nature, stabilized by intermolecular interactions. ADG-HPMC-AS MPs displayed minimal drug release under acidic medium, while drug release was observed up to 24 h in colonic milieu. Later, therapeutic efficacy of ADG-HPMC-AS MPs was tested against TNBS-induced UC and demonstrated superior efficacy in DAI and CMDI scores. ADG-HPMC-AS MPs caused significant (P ≤ 0.0001) down-regulation of NF-κB (0.75-fold), STAT3 (2.12-fold), and p-STAT3 (1.15-fold) expression relative to positive control. ADG-HPMC-AS MPs produced marked suppression of mRNA expression (IL-1β, IL-6, TNF-α, COX-2, iNOS, and MMP-9) in TNBS-induced UC. ADG-HPMC-AS MPs-treated group markedly ameliorated epithelial damage, inflammatory infiltration, and collagen deposition, demonstrating lowest histopathological scores compared to positive control. These findings validate ADG-HPMC-AS MPs as a drug delivery system that ameliorates UC by attenuating oxidative stress and NF-kB/STAT3-driven signalling. In conclusion, ADG-HPMC-AS MPs may serve as a promising drug-delivery system for improving the therapeutic potential of ADG in the effective management of UC.