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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.

Hussain Z, Katas H, Mohd Amin MC, Kumolosasi E - PLoS ONE (2014)

Bottom Line: 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).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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

ABSTRACT
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.

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Histological stabilization of NP-based formulation.Histological photomicrographs of AD-like skin lesions of NC/Nga mice treated with NP-based formulations compared to normal/baseline mice and treatment groups. Arrows indicate the magnitude of collagen fibers deposition. Note that collagen fibers were stained green by Masson's trichrome. Photomicrographs were imaged under ×100-µm magnification. AD, atopic dermatitis; NPs, nanoparticles.
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pone-0113143-g007: Histological stabilization of NP-based formulation.Histological photomicrographs of AD-like skin lesions of NC/Nga mice treated with NP-based formulations compared to normal/baseline mice and treatment groups. Arrows indicate the magnitude of collagen fibers deposition. Note that collagen fibers were stained green by Masson's trichrome. Photomicrographs were imaged under ×100-µm magnification. AD, atopic dermatitis; NPs, nanoparticles.

Mentions: Processed skin specimens were also stained with Masson's trichrome to explore anatomical and histological changes produced in collagen fibers. Results obtained are presented in Fig. 7 as photomicrographs representing degree of collagen scaffold deposition (acquiring green color with Masson's trichrome) in the dermis. NG-CONT mice had shown highest deposition of collagen fibers in papillary and reticular layers of the dermis. Moreover, the atopic mice were also presented with the highest number of fibroblasts in the reticular dermis, with significant damage to the epidermal layers was also observed. These conditions could be explained by repeated topical applications of DNFB that led to fibrogenesis with elevated production and deposition of collagen fibers in the dermal layers. Similarly, VGRs also showed similar deposition of collagen fibers and number of fibroblast as observed in the atopic mice group. Processed skin sections of POS-CONT showed considerably lower degree of collagen fibers deposited in the papillary dermal layer because HC suppressed fibrogenesis and infiltration of fibroblasts. Mice treated with non-NPs–based formulations demonstrated greater control of fibroblast infiltration, although higher collagen fibers deposition was observed compared to POS-CONT mice as shown in Fig. 7. On the other hand, when mice were treated with co-loaded NP-based formulations, a remarkably lower degree of fibrogenesis and number of infiltrated fibroblasts was observed. The finding of a lower number of fibroblasts is expected to play a key role in reducing tissue remodeling, skin fibrosis, and scar formation secondary to AD-like skin lesions. The lowering effect of NP-based formulations might be due to synergistic actions of HC, HT, and CS to alleviate underlying inflammatory reactions involved in initiating fibrogenesis. Fig. 7 also shows a photomicrograph of baseline mice, demonstrating the presence of well-developed hair follicles and normal deposition of collagen fibers responsible for maintaining skin texture and integrity.


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.

Hussain Z, Katas H, Mohd Amin MC, Kumolosasi E - PLoS ONE (2014)

Histological stabilization of NP-based formulation.Histological photomicrographs of AD-like skin lesions of NC/Nga mice treated with NP-based formulations compared to normal/baseline mice and treatment groups. Arrows indicate the magnitude of collagen fibers deposition. Note that collagen fibers were stained green by Masson's trichrome. Photomicrographs were imaged under ×100-µm magnification. AD, atopic dermatitis; NPs, nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232601&req=5

pone-0113143-g007: Histological stabilization of NP-based formulation.Histological photomicrographs of AD-like skin lesions of NC/Nga mice treated with NP-based formulations compared to normal/baseline mice and treatment groups. Arrows indicate the magnitude of collagen fibers deposition. Note that collagen fibers were stained green by Masson's trichrome. Photomicrographs were imaged under ×100-µm magnification. AD, atopic dermatitis; NPs, nanoparticles.
Mentions: Processed skin specimens were also stained with Masson's trichrome to explore anatomical and histological changes produced in collagen fibers. Results obtained are presented in Fig. 7 as photomicrographs representing degree of collagen scaffold deposition (acquiring green color with Masson's trichrome) in the dermis. NG-CONT mice had shown highest deposition of collagen fibers in papillary and reticular layers of the dermis. Moreover, the atopic mice were also presented with the highest number of fibroblasts in the reticular dermis, with significant damage to the epidermal layers was also observed. These conditions could be explained by repeated topical applications of DNFB that led to fibrogenesis with elevated production and deposition of collagen fibers in the dermal layers. Similarly, VGRs also showed similar deposition of collagen fibers and number of fibroblast as observed in the atopic mice group. Processed skin sections of POS-CONT showed considerably lower degree of collagen fibers deposited in the papillary dermal layer because HC suppressed fibrogenesis and infiltration of fibroblasts. Mice treated with non-NPs–based formulations demonstrated greater control of fibroblast infiltration, although higher collagen fibers deposition was observed compared to POS-CONT mice as shown in Fig. 7. On the other hand, when mice were treated with co-loaded NP-based formulations, a remarkably lower degree of fibrogenesis and number of infiltrated fibroblasts was observed. The finding of a lower number of fibroblasts is expected to play a key role in reducing tissue remodeling, skin fibrosis, and scar formation secondary to AD-like skin lesions. The lowering effect of NP-based formulations might be due to synergistic actions of HC, HT, and CS to alleviate underlying inflammatory reactions involved in initiating fibrogenesis. Fig. 7 also shows a photomicrograph of baseline mice, demonstrating the presence of well-developed hair follicles and normal deposition of collagen fibers responsible for maintaining skin texture and integrity.

Bottom Line: 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).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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus