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

https://doi.org/10.1016/j.nano.2020.102292Get rights and content

Highlights

  • •

    Chrysin-loaded PLGA attenuates experimental allergic asthma.

  • •

    Chrysin-loaded PLGA modulates TLR/NF-κB,

  • •

    Chrysin-loaded PLGA regulates inflammasome activation.

Abstract

Asthma, one of the significant public health problems, is triggered by certain inflammatory processes in the airways that are not addressed propitiously by current therapies. Though pieces of evidence on allergic asthma mitigation by the anti-inflammatory bioflavonoid chrysin (CHR) are accumulating, poor bioavailability, and low solubility curtail drug development. To overcome these shortcomings, CHR loaded nanoparticle (CHR-NP) was formulated, and its salutary effect in preclinical murine allergic asthma model via the peroral route was evaluated. The spherical nanosized particles showed slow, sustained release in vitro. Moreover, CHR-NP dramatically reduced the serum IgE, ovalbumin (OVA)-induced lung histological alteration, as well as Th2 (T-helper 2) cytokines in the bronchoalveolar lavage fluid (BALF). It also suppressed the elevated serum pro-inflammatory cytokines and their upstream TLR/NF-κB/NLRP3 pathway activation in lung superior to CHR and almost identical to dexamethasone (DEX). Thus this study suggests the potentiality of CHR-NP in ameliorating allergic asthma progression.

Graphical Abstract

Chrysin-loaded PLGA nanoparticles (CHR-NP) was formulated to enhance the bioavailability of Chrysin. Hence higher therapeutic efficacy compared to free Chrysin (CHR) was observed in vivo. CHR-NP was fed orally to asthmatic mice, which has inflamed lung along with elevated Th2 cytokines and IgE levels. The probable mechanistic pathway via which the CHR was able to suppress allergic asthma associated inflammation and thereby mitigate the disease condition is also illustrated in this study.

Unlabelled Image
  1. Download : Download high-res image (266KB)
  2. Download : Download full-size image

Section snippets

Materials

Chrysin (CHR) (purity ≥97.0%), Dexamethasone (Dex), PLGA (85:15), Fluorescein isothiocyanate (FITC) and 4,6 -diamidino-2-phenylindole (DAPI), Fetal bovine serum (FBS) was purchased from Sigma Aldrich (MO, USA). The primary and secondary antibodies were obtained from Santa Cruz Biotechnology (Santa Cruz, CA). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) analysis was done by commercial assay kits. (BioVision, Milpitas, CA, USA). The cytokines level was measured by

Morphological analysis of CHR-NPs

The TEM and AFM images showed CHR-NPs to be spherical, and size was (65–90) nm in TEM (Figure 1, A) and 77 nm in AFM, respectively. The particle size distribution obtained from the TEM image was undiversified and at par with DLS result. The AFM image of CHR-NPs revealed a smooth spherical structure at high resolution in two and three dimensions. (Figure 1, B).

Physiochemical characterization of CHR-NP

DSC study showed a thermogram of pure CHR having a sharp endothermic peak at 293.5 °C while that of B-NP at 51 °C corresponding to its

Discussion

In our study, the CHR loaded PLGA nanoparticle (CHR-NP) formulated utilizing nanoprecipitation technique, were spherically shaped without any noticeable surface ridges. Furthermore, DSC and XRD analysis indicated the inclusion of CHR inside the polymer matrix. The FTIR spectra were consistent with the other physicochemical characterization data verifying no free CHR to be present on the nanoparticle surface.

The CHR-NP with <100 nm size showed a sustained or gradual pattern of drug-release and

References (47)

  • K. Tahara et al.

    Improved cellular uptake of chitosan-modified PLGA nanospheres by A549 cells

    Int J Pharm

    (2009)
  • S. Acharya et al.

    PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect

    Adv Drug Deliv Rev

    (2011)
  • F. Martinon et al.

    The Inflammasome: a molecular platform triggering activation of inflammatory Caspases and processing of pro IL-beta

    Mol Cell

    (2002)
  • M.M. Yallapu et al.

    Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells

    J Colloid Interface Sci

    (2010)
  • The Global Asthma Report

    Auckland

    (2018)
  • D. Agrawal et al.

    Pathogenesis of allergic airway inflammation

    Curr Allergy Asthma Rep

    (2010)
  • C.E. Brightling et al.

    Mast-cell infiltration of airway smooth muscle in asthma

    N Engl J Med

    (2002)
  • H. Nakajima et al.

    Role of cytokines in allergic airway inflammation

    Int Arch Allergy Immunol

    (2007)
  • H.K. Reddel et al.

    A fundamental change in asthma management

    Eur Respir J

    (2019)
  • J.M. Foster et al.

    Personality influences the reporting of side effects of inhaled corticosteroids in asthma patients

    J Asthma

    (2008)
  • R.S. Irwin et al.

    Side effects with inhaled corticos-teroids: the physician's perception

    Chest

    (2006)
  • H. Cho et al.

    Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives

    Pharmacol. Res.

    (2004)
  • K. Noh et al.

    Pharmacokinetic interaction of Chrysin with caffeine in rats

    Biomol Ther

    (2016)

    • Cited by (0)

    Funding Source: This work was supported by the National Medicinal Plant Board (NMPB), Ministry of AYUSH & Department of Biotechnology, North Eastern Region (DBT-NER), Government of India partially along with a research fellowship of ICMR-SRF granted by the Indian Council of Medical Research (ICMR), Government of India.

    Disclosure: The authors of this article declare no conflicts of interest.

    View full text
    © 2020 Elsevier Inc. All rights reserved.