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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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Anti-AD efficacy of NPs-based formulations.Effect of NP-based formulations on the expression of IgE, histamine, PGE2, and VEGF-α in serum (A1, B1, C1, and D1) and skin tissue homogenates (A2, B2, C2, and D2) of AD-induced NC/Nga mice groups compared to other groups tested. Data are presented as mean ± S.D of triplicate experiments; ##p<0.005 baseline vs. atopic mice, and **p<0.005 NP-based formulations vs. atopic/VGRs groups. AD, atopic dermatitis; IgE, immunoglobulin-E; NPs, nanoparticles; PGE2, prostaglandin-E2; VEGF-α, vascular endothelial growth factor-α; VGRs, vehicle groups.
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pone-0113143-g003: Anti-AD efficacy of NPs-based formulations.Effect of NP-based formulations on the expression of IgE, histamine, PGE2, and VEGF-α in serum (A1, B1, C1, and D1) and skin tissue homogenates (A2, B2, C2, and D2) of AD-induced NC/Nga mice groups compared to other groups tested. Data are presented as mean ± S.D of triplicate experiments; ##p<0.005 baseline vs. atopic mice, and **p<0.005 NP-based formulations vs. atopic/VGRs groups. AD, atopic dermatitis; IgE, immunoglobulin-E; NPs, nanoparticles; PGE2, prostaglandin-E2; VEGF-α, vascular endothelial growth factor-α; VGRs, vehicle groups.

Mentions: The untreated atopic mice group expressed the highest level of IgE in serum (1282±72 ng/mL) and skin homogenates (876±64 ng/mL) as shown in Fig. 3 [A1] and Fig. 3 [A2], respectively. These results were in accordance with previously published reports [38], [39]. They suggested that the high level of IgE measured in this group could be associated with activation of underlying inflammatory cascades in response to repetitive applications of DNFB. As a result, class switching of B-lymphocytes provokes higher expression of local and systemic IgE that leads to severe dermatosis in the atopic group. VGRs also had high levels of IgE in both samples. In contrast, commercial DermAid 0.5% cream suppressed IgE to 767±38 ng/mL and 642±74 ng/mL in serum and skin homogenates, respectively. On the other hand, co-loaded NP-based formulations demonstrated remarkable control of IgE expression (**p<0.005, one-way ANOVA), which was more prominent in the skin homogenates. The anti-IgE effect of NP-based formulations was attributable to the synergistic action of co-loaded drugs to mitigate the progression of the underlying adaptive immune response involved in AD. Furthermore, improved control of IgE expression in the skin tissues was expected to be associated with the role of CS in retaining therapeutic concentrations of both drugs in the epidermis and dermis.


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)

Anti-AD efficacy of NPs-based formulations.Effect of NP-based formulations on the expression of IgE, histamine, PGE2, and VEGF-α in serum (A1, B1, C1, and D1) and skin tissue homogenates (A2, B2, C2, and D2) of AD-induced NC/Nga mice groups compared to other groups tested. Data are presented as mean ± S.D of triplicate experiments; ##p<0.005 baseline vs. atopic mice, and **p<0.005 NP-based formulations vs. atopic/VGRs groups. AD, atopic dermatitis; IgE, immunoglobulin-E; NPs, nanoparticles; PGE2, prostaglandin-E2; VEGF-α, vascular endothelial growth factor-α; VGRs, vehicle groups.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0113143-g003: Anti-AD efficacy of NPs-based formulations.Effect of NP-based formulations on the expression of IgE, histamine, PGE2, and VEGF-α in serum (A1, B1, C1, and D1) and skin tissue homogenates (A2, B2, C2, and D2) of AD-induced NC/Nga mice groups compared to other groups tested. Data are presented as mean ± S.D of triplicate experiments; ##p<0.005 baseline vs. atopic mice, and **p<0.005 NP-based formulations vs. atopic/VGRs groups. AD, atopic dermatitis; IgE, immunoglobulin-E; NPs, nanoparticles; PGE2, prostaglandin-E2; VEGF-α, vascular endothelial growth factor-α; VGRs, vehicle groups.
Mentions: The untreated atopic mice group expressed the highest level of IgE in serum (1282±72 ng/mL) and skin homogenates (876±64 ng/mL) as shown in Fig. 3 [A1] and Fig. 3 [A2], respectively. These results were in accordance with previously published reports [38], [39]. They suggested that the high level of IgE measured in this group could be associated with activation of underlying inflammatory cascades in response to repetitive applications of DNFB. As a result, class switching of B-lymphocytes provokes higher expression of local and systemic IgE that leads to severe dermatosis in the atopic group. VGRs also had high levels of IgE in both samples. In contrast, commercial DermAid 0.5% cream suppressed IgE to 767±38 ng/mL and 642±74 ng/mL in serum and skin homogenates, respectively. On the other hand, co-loaded NP-based formulations demonstrated remarkable control of IgE expression (**p<0.005, one-way ANOVA), which was more prominent in the skin homogenates. The anti-IgE effect of NP-based formulations was attributable to the synergistic action of co-loaded drugs to mitigate the progression of the underlying adaptive immune response involved in AD. Furthermore, improved control of IgE expression in the skin tissues was expected to be associated with the role of CS in retaining therapeutic concentrations of both drugs in the epidermis and dermis.

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