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


CONCLUSIONS
The current investigation suggests that NP-mediated transcutaneous delivery of HC could be considered an effective therapeutic approach to manage dermatitis.
Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Zahid
Z
Hussain
Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Haliza
H
Katas
Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Mohd Cairul Iqbal
MC
Mohd Amin
Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Endang
E
Kumolosasi
Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, Selangor, Malaysia.
Shariza
S
Sahudin
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000633:toxicity; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011897:Random Allocation
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004337:Drug Carriers; D048271:Chitosan; D004139:Dinitrofluorobenzene; D006854:Hydrocortisone
chitosan nanocarrier; elastic fibers; glucocorticoids; topical delivery