PLGA-Loaded Monascin Intranasal Delivery System: Sustained-Release and Immunomodulatory Effect for Treatment of Allergic Rhinitis by Improving Regulatory T Cell Function.

Abstract

Monascin, a natural and safe drug, exhibits potent anti-inflammatory, hypolipidemic, and antioxidative effects. However, their therapeutic potential and underlying mechanisms in allergic rhinitis (AR) remain unexplored. The intranasal delivery of monascin for treating AR faces the challenge of rapid clearance. Herein, to achieve sustained and prolonged release, we developed monascin-encapsulated poly(lactic co glycolic acid) nanoparticles (PLGA-MS) by the mechanical double emulsion technique, enabling effective local delivery of monascin for the treatment of AR. Histopathological staining, flow cytometry, ELISA, and network pharmacology were used to assess therapeutic effects and potential mechanisms of monascin in treating AR. In vitro and in vivo experiments revealed that PLGA-MS exhibited enhanced stability, excellent drug encapsulation capacity, and sustained drug release. PLGA-MS treatment showed a significant therapeutic effect in AR mice by decreasing inflammatory cells in nasal tissue and regulating IgE, histamine, and a variety of cytokines. PLGA-MS treatment decreased T helper 2 cells (Th2) and T helper 17 cells (Th17) while promoting and increasing Tregs (regulatory T cells). Further analysis showed elevated levels of IL-10 and TGF-β expression in Tregs post-treatment. Results of the CCK-8 assay, pathological analysis of vital organs, and serum analysis of liver and kidney functions demonstrated the biosafety of PLGA-MS. Additionally, network pharmacology identified immune response pathways that may support PLGA-MS's immunomodulatory effects in AR. Our study presented a biomaterial-facilitated intranasal delivery system for monascin, offering an effective therapeutic strategy for AR.