Chrysin-loaded PLGA attenuates OVA-induced allergic asthma by modulating TLR/NF-κB/NLRP3 axis

Area of Science:

• * Pharmacology and Nanotechnology
• * Immunology and Respiratory Medicine

Background:

• * Asthma is a prevalent respiratory condition driven by airway inflammation, with current treatments having limitations.
• * Chrysin (CHR), a bioflavonoid, shows anti-inflammatory potential for allergic asthma but suffers from poor bioavailability and solubility.
• * Nanoparticle formulation is explored to enhance CHR delivery and efficacy.

Purpose of the Study:

• * To formulate and evaluate chrysin-loaded nanoparticles (CHR-NP) for the treatment of allergic asthma.
• * To assess the in vitro release profile and in vivo therapeutic effects of CHR-NP via oral administration.
• * To investigate the impact of CHR-NP on key inflammatory markers and pathways in a preclinical asthma model.

Main Methods:

• * Formulation of spherical, nanosized chrysin-loaded nanoparticles (CHR-NP) with sustained in vitro release.
• * Evaluation of CHR-NP in a murine model of ovalbumin (OVA)-induced allergic asthma.
• * Measurement of serum IgE, bronchoalveolar lavage fluid (BALF) Th2 cytokines, serum pro-inflammatory cytokines, and TLR/NF-κB/NLRP3 pathway activation.

Main Results:

• * CHR-NP exhibited slow and sustained drug release in vitro.
• * CHR-NP significantly reduced serum IgE levels and OVA-induced lung histological damage.
• * CHR-NP suppressed Th2 cytokines in BALF and attenuated pro-inflammatory cytokine signaling via the TLR/NF-κB/NLRP3 pathway, outperforming free CHR and nearing dexamethasone efficacy.

Conclusions:

• * Chrysin-loaded nanoparticles (CHR-NP) demonstrate significant potential for ameliorating allergic asthma progression.
• * The oral delivery of CHR-NP offers a viable strategy to overcome the bioavailability limitations of chrysin.
• * CHR-NP effectively modulates key inflammatory pathways involved in allergic asthma pathogenesis.