Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles

Int J Nanomedicine. 2014 Nov 5:9:5143-56. doi: 10.2147/IJN.S71543. eCollection 2014.

Abstract

Background: Atopic dermatitis is a chronic, noncontiguous, and exudative disorder accompanied by perivascular infiltration of immune mediators, including T-helper (Type 1 helper/Type 2 helper) cells, mast cells, and immunoglobulin E. The current study explores the immunomodulatory and histological effects of nanoparticle (NP)-based transcutaneous delivery of hydrocortisone (HC).

Methods: In this study, HC, the least potent topical glucocorticoid, was administered transcutaneously as chitosan NPs. The pharmacological and immunological effects of the NP-based HC delivery on the alleviation of 2,4-dinitrofluorobenzene-induced atopic dermatitis (AD)-like skin lesions were evaluated using the NC/Nga mouse model.

Results: In vivo Dino-Lite(®) microscopic assessment revealed that the NP-based formulation displayed a remarkable ability to reduce the severity of the pathological features of AD (dermatitis index, 3.0). The AD suppressive activity of the NP-based topical formulation was expected owing to the interruption of a series of immunopathological events, including the production of immunoglobulin E, release of histamine, and expression of prostaglandin-E2 and vascular endothelial growth factor-α in the sera and skin of the tested animals. Analysis of the cytokine expression in AD-like skin lesions further revealed that the NP-based formulation inhibited the pathological expression of interleukin (IL)-4, IL-5, IL-6, IL-13, IL-12p70, interferon-γ, and tumor necrosis factor-α in serum and skin homogenates of NC/Nga mice. Further, our histological findings indicated that the NP-based formulation inhibited fibroblast infiltration and fragmentation of elastic fibers, further supporting the clinical importance of these formulations in maintaining the integrity of elastic connective tissues.

Conclusion: The current investigation suggests that NP-mediated transcutaneous delivery of HC could be considered an effective therapeutic approach to manage dermatitis.

Keywords: chitosan nanocarrier; elastic fibers; glucocorticoids; topical delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / chemistry
  • Chitosan / chemistry
  • Cytokines / analysis
  • Cytokines / metabolism
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology*
  • Dinitrofluorobenzene / toxicity
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry*
  • Hydrocortisone / administration & dosage*
  • Hydrocortisone / chemistry
  • Mice
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Random Allocation

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Drug Carriers
  • Chitosan
  • Dinitrofluorobenzene
  • Hydrocortisone