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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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Clinical effectiveness of NP-based formulations compared to other groups tested.Digital images (A) and ADI (B) of untreated and treated AD-induced NC/Nga mice. Digital images represent the severity of AD symptoms at the end of treatment in term of ADI. AD, atopic dermatitis; ADI, atopic dermatitis index/scores; NP, nanoparticles. **Digital images were taken from the same animals as previously reported in Hussain et al. [3].
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pone-0113143-g002: Clinical effectiveness of NP-based formulations compared to other groups tested.Digital images (A) and ADI (B) of untreated and treated AD-induced NC/Nga mice. Digital images represent the severity of AD symptoms at the end of treatment in term of ADI. AD, atopic dermatitis; ADI, atopic dermatitis index/scores; NP, nanoparticles. **Digital images were taken from the same animals as previously reported in Hussain et al. [3].

Mentions: Therapeutic effectiveness of NP-based formulations using an NC/Nga mouse model was explored by examining its representative symptom, dermatosis severity. Severity of AD was assessed by 2 dermatologists blind to groups tested according to the criteria described previously by Park et al. [37]. The severity of AD was evaluated as AD index/score (ADI) established according to the following criteria: (1) erythema/hemorrhage, (2) dryness/scaling, (3) edema/swelling, and (4) erosion/excoriation, each of which were scored as 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The sum of the individual scores was then taken as the ADI. Fig. 2 addressed that AD-induced mice that had not received any treatment (NG-CONT) had shown highest severity of dermatosis (ADI, 10.5). The obtained image of NG-CONT mice had shown various pathological features such as severe erythema, hemorrhage, edema, release of exudates/transudates, superficial erosion, deep excoriation, intense itching, and dry skin (Fig. 2 [A]). The obtained digital photographs also highlighted that the severity of dermatosis in VGR groups (Q-VGR and A-VGR) was similar to the NG-CONT group, but with reduced hemorrhage, edema, and erythema. In contrast, AD-induced mice treated with commercial DermAid 0.5% formulation (POS-CONT) had better control of AD symptoms (ADI, 7.0). On the other hand, NP-based formulations demonstrated remarkable control of AD symptoms compared to non-NPs–based formulations. The ADI of Q-HC-HT-NPs and A-HC-HT-NPs were significantly lower than Q-HC-HT-cream and A-HC-HT-cream as shown Fig. 2 [B]. Furthermore, QV-based NPs formulation was more effective in controlling the severity of dermatosis compared with aqueous-based NPs formulation. This finding could be related to the higher drug permeation flux across the NC/Nga mouse skin when the drugs were incorporated into QV-cream (S2). Higher contents of glycerol, light liquid paraffin and white soft paraffin in QV-cream compared to aqueous cream higher might attribute to higher drug permeation flux. QV-cream also provides better skin hydration that facilitates drug permeation across the skin. Besides, natural oil such as squalene, stearic acid and stearyl alcohol could further improve drug permeation by improving adhesiveness of QV-cream on the skin. Therefore, these findings suggested that NP-based formulations were more effective in maintaining skin integrity during the course of dermatosis and treatment, and were associated with minimal symptoms of dryness and erythema.


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)

Clinical effectiveness of NP-based formulations compared to other groups tested.Digital images (A) and ADI (B) of untreated and treated AD-induced NC/Nga mice. Digital images represent the severity of AD symptoms at the end of treatment in term of ADI. AD, atopic dermatitis; ADI, atopic dermatitis index/scores; NP, nanoparticles. **Digital images were taken from the same animals as previously reported in Hussain et al. [3].
© Copyright Policy
Related In: Results  -  Collection

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

pone-0113143-g002: Clinical effectiveness of NP-based formulations compared to other groups tested.Digital images (A) and ADI (B) of untreated and treated AD-induced NC/Nga mice. Digital images represent the severity of AD symptoms at the end of treatment in term of ADI. AD, atopic dermatitis; ADI, atopic dermatitis index/scores; NP, nanoparticles. **Digital images were taken from the same animals as previously reported in Hussain et al. [3].
Mentions: Therapeutic effectiveness of NP-based formulations using an NC/Nga mouse model was explored by examining its representative symptom, dermatosis severity. Severity of AD was assessed by 2 dermatologists blind to groups tested according to the criteria described previously by Park et al. [37]. The severity of AD was evaluated as AD index/score (ADI) established according to the following criteria: (1) erythema/hemorrhage, (2) dryness/scaling, (3) edema/swelling, and (4) erosion/excoriation, each of which were scored as 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The sum of the individual scores was then taken as the ADI. Fig. 2 addressed that AD-induced mice that had not received any treatment (NG-CONT) had shown highest severity of dermatosis (ADI, 10.5). The obtained image of NG-CONT mice had shown various pathological features such as severe erythema, hemorrhage, edema, release of exudates/transudates, superficial erosion, deep excoriation, intense itching, and dry skin (Fig. 2 [A]). The obtained digital photographs also highlighted that the severity of dermatosis in VGR groups (Q-VGR and A-VGR) was similar to the NG-CONT group, but with reduced hemorrhage, edema, and erythema. In contrast, AD-induced mice treated with commercial DermAid 0.5% formulation (POS-CONT) had better control of AD symptoms (ADI, 7.0). On the other hand, NP-based formulations demonstrated remarkable control of AD symptoms compared to non-NPs–based formulations. The ADI of Q-HC-HT-NPs and A-HC-HT-NPs were significantly lower than Q-HC-HT-cream and A-HC-HT-cream as shown Fig. 2 [B]. Furthermore, QV-based NPs formulation was more effective in controlling the severity of dermatosis compared with aqueous-based NPs formulation. This finding could be related to the higher drug permeation flux across the NC/Nga mouse skin when the drugs were incorporated into QV-cream (S2). Higher contents of glycerol, light liquid paraffin and white soft paraffin in QV-cream compared to aqueous cream higher might attribute to higher drug permeation flux. QV-cream also provides better skin hydration that facilitates drug permeation across the skin. Besides, natural oil such as squalene, stearic acid and stearyl alcohol could further improve drug permeation by improving adhesiveness of QV-cream on the skin. Therefore, these findings suggested that NP-based formulations were more effective in maintaining skin integrity during the course of dermatosis and treatment, and were associated with minimal symptoms of dryness and erythema.

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