Biopolymer-stabilized zein nanoparticles for pressure ulcer management: Formulation, optimization, and preliminary in vivo assessment.

Pressure ulcers (PUs) remain a major healthcare burden, requiring innovative, safe, and effective therapies. Bioactive polysaccharide-based nanoplatforms offer promise owing to their biocompatibility, biodegradability, and wound-healing potential. This study aimed to develop and optimize zein nanoparticles (ZnNPs) stabilized with natural bioactive polysaccharides-Tragacanth (TG), Dextran sodium sulphate (Dx), Pectin (Pec), or Acacia (Ac)-for PU management. Formulations were optimized by varying Zn: biopolymer ratio, order of mixing, and polymer type, then characterized by colloidal properties, TEM, and stability testing. To assess additive therapeutic effects, Naringenin (NAR) was incorporated into ZnTGNPs. All optimized systems were further evaluated in vivo in a PU rat model through wound contraction and histopathology. Results revealed that TG-stabilized ZnNPs (Zn TG NPs) exhibited superior characteristics (167± 1.5 nm, 0.25± 0.06 & -33 mV) and significant three-month stability. The incorporation of NAR into Zn TG NPs resulted in 98% encapsulation efficiency and controlled release over 48 h. In vivo evaluation demonstrated that both drug-free and NAR-loaded Zn TG NPs promoted significant wound closure and histological regeneration compared with controls. Interestingly, drug-free Zn TG NPs achieved healing efficacy comparable to their drug-loaded counterparts, underscoring the intrinsic bioactivity of TG in supporting tissue repair. These findings support the potential of biopolymer-based nanoplatforms as effective, drug-free treatments for pressure ulcers, offering a safe and sustainable alternative to conventional medicated therapies. Further long-term and mechanistic studies are warranted to confirm their translational potential in clinical wound care.