Abstract
Allergic rhinitis (AR) is a common inflammatory condition requiring innovative therapeutic approaches. This study introduces a nanocomposite hydrogel system combining Arnica montana extract and propolis-loaded chitosan nanoparticles (AMEPROCNPs) with menstrual blood-derived mesenchymal stem cells (MenSCs), designed for sustained delivery and enhanced mucosal healing. The system demonstrated biocompatibility, effective drug release, and strong mucoadhesion. In vitro studies showed marked reductions in pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, alongside significant cytoprotection against oxidative stress. In vivo, the optimized formulation (HYDROMenSC-CNP-8) substantially alleviated AR symptoms and significantly downregulated key Th2-associated cytokines (IL-4, IL-5, IL-13) and TNF-α, while upregulating IFN-γ levels, comparable to Fluticasone Propionate. These results suggest that the AMEPROCNPs-loaded MenSC-collagen hydrogel represents a promising, safe, and effective alternative to current AR therapies. Furthermore, this system holds potential for broader application in treating other inflammatory and allergic diseases.