Efficient immuno-modulation of TH1/TH2 biomarkers in 2,4-dinitrofluorobenzene-induced atopic dermatitis: nanocarrier-mediated transcutaneous co-delivery of anti-inflammatory and antioxidant drugs.
The present study was conducted with the aim to investigate the immuno-modulatory and histological stabilization effects of nanocarrier-based transcutaneous co-delivery of hydrocortisone (HC) and hydroxytyrosol (HT). In this investigation, the clinical and pharmacological efficacies of nanoparticle (NP)-based formulation to alleviate 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) was explored by using an NC/Nga mouse model. Ex vivo visual examination of AD induction in experimental mice indicated remarkable control of NP-based formulations in reducing pathological severity of AD-like skin lesions. Therapeutic effectiveness of NP-based formulations was also evaluated by comparing skin thickness of AD-induced NP-treated mice (456±27 µm) with that of atopic mice (916±37 µm). Analysis of the immuno-spectrum of AD also revealed the dominance of NP-based formulations in restraining immunoglobulin-E (IgE), histamine, prostaglandin-E2 (PGE2), vascular endothelial growth factor-α (VEGF-α), and T-helper cells (TH1/TH2) producing cytokines in serum and skin biopsies of tested mice. These anti-AD data were further supported by histological findings that revealed alleviated pathological features, including collagen fiber deposition, fibroblasts infiltration, and fragmentation of elastic fibers in experimental mice. Thus, NP-mediated transcutaneous co-delivery of HC and HT can be considered as a promising therapy for managing immunological and histological spectra associated with AD.
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
D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000633:toxicity; D015232:Dinoprostone / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D006632:Histamine / Q000032:analysis / Q000097:blood; D006854:Hydrocortisone / Q000008:administration & dosage; D007073:Immunoglobulin E / Q000032:analysis / Q000097:blood; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives; D012867:Skin / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000097:blood
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D004337:Drug Carriers; D042461:Vascular Endothelial Growth Factor A; C005975:3,4-dihydroxyphenylethanol; D007073:Immunoglobulin E; D006632:Histamine; D004139:Dinitrofluorobenzene; D015232:Dinoprostone; D010626:Phenylethyl Alcohol; D006854:Hydrocortisone