Limits...
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.

Show MeSH

Related in: MedlinePlus

Flow characteristics of NP- and non-NP-based formulations.Rheogram of QV and aqueous NP-based formulations (A), Rheogram of QV and aqueous non-NPs–based formulations (B), apparent viscosities of NP- and non-NP–based formulations (C). Results represent the non-Newtonian mechanics of NPs- and non-NPs-based formulations. NPs, nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4232601&req=5

pone-0113143-g001: Flow characteristics of NP- and non-NP-based formulations.Rheogram of QV and aqueous NP-based formulations (A), Rheogram of QV and aqueous non-NPs–based formulations (B), apparent viscosities of NP- and non-NP–based formulations (C). Results represent the non-Newtonian mechanics of NPs- and non-NPs-based formulations. NPs, nanoparticles.

Mentions: Rheological property is an imperative parameter in the comprehension of flow characteristics and colloidal stability of formulations [31]. Rheograms of QV- and aqueous-based non-NP- and NP-based formulations are shown in Fig. 1. The rate and extent of shear stress on the QV- and aqueous-based NP-based formulations were proportionally dependent on the applied strain rates (Fig. 1 [A]). Furthermore, they demonstrated pseudoplastic flow. These results are in accordance with a previous study [32], which described that the rate and extent of shear stress of any formulation proportionally correlated with the applied strain rate would follow non-Newtonian mechanics. Furthermore, the QV-based co-loaded NPs-based formulation was observed to be more thixotropic in nature compared to the aqueous-based formulation. Thixotropy and viscosity greatly influence release rate of drugs from the cream matrices, occlusiveness and bio-adhesion of creams when they are applied onto the skin [33]. Higher thixotropy and viscosity improve adhesiveness of a cream for a longer period of time and thus, enhance its efficacy [33]. In present study, QV-cream had shown slightly higher thixotropy and viscosity compared to the aqueous cream that might also increase intimate contact between the release NPs and the skin that led to higher anti-AD efficacy of QV-based NPs formulations compared with aqueous-based ones. Besides, the viscosity and thixotropy of topical cream influence the spreadability and permeation of drugs into the epidermis and dermis [34]. On the other hand, the non-NPs-based formulations had also demonstrated non-Newtonian mechanics with similar flow characteristics between QV- and aqueous-based systems (Fig. 1 [B]). Moreover, QV- and aqueous-based co-loaded NPs-based formulations were more found to be more thixotropic compared to non-NPs-based formulations. The authors described that the increase in shear stress observed with increasing of strain rate was expected to be due to structural breakdown of weak bonds that hold particulate matters together [35]. This might lead to the formation of aggregates and reduce apparent viscosity.


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)

Flow characteristics of NP- and non-NP-based formulations.Rheogram of QV and aqueous NP-based formulations (A), Rheogram of QV and aqueous non-NPs–based formulations (B), apparent viscosities of NP- and non-NP–based formulations (C). Results represent the non-Newtonian mechanics of NPs- and non-NPs-based formulations. NPs, nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0113143-g001: Flow characteristics of NP- and non-NP-based formulations.Rheogram of QV and aqueous NP-based formulations (A), Rheogram of QV and aqueous non-NPs–based formulations (B), apparent viscosities of NP- and non-NP–based formulations (C). Results represent the non-Newtonian mechanics of NPs- and non-NPs-based formulations. NPs, nanoparticles.
Mentions: Rheological property is an imperative parameter in the comprehension of flow characteristics and colloidal stability of formulations [31]. Rheograms of QV- and aqueous-based non-NP- and NP-based formulations are shown in Fig. 1. The rate and extent of shear stress on the QV- and aqueous-based NP-based formulations were proportionally dependent on the applied strain rates (Fig. 1 [A]). Furthermore, they demonstrated pseudoplastic flow. These results are in accordance with a previous study [32], which described that the rate and extent of shear stress of any formulation proportionally correlated with the applied strain rate would follow non-Newtonian mechanics. Furthermore, the QV-based co-loaded NPs-based formulation was observed to be more thixotropic in nature compared to the aqueous-based formulation. Thixotropy and viscosity greatly influence release rate of drugs from the cream matrices, occlusiveness and bio-adhesion of creams when they are applied onto the skin [33]. Higher thixotropy and viscosity improve adhesiveness of a cream for a longer period of time and thus, enhance its efficacy [33]. In present study, QV-cream had shown slightly higher thixotropy and viscosity compared to the aqueous cream that might also increase intimate contact between the release NPs and the skin that led to higher anti-AD efficacy of QV-based NPs formulations compared with aqueous-based ones. Besides, the viscosity and thixotropy of topical cream influence the spreadability and permeation of drugs into the epidermis and dermis [34]. On the other hand, the non-NPs-based formulations had also demonstrated non-Newtonian mechanics with similar flow characteristics between QV- and aqueous-based systems (Fig. 1 [B]). Moreover, QV- and aqueous-based co-loaded NPs-based formulations were more found to be more thixotropic compared to non-NPs-based formulations. The authors described that the increase in shear stress observed with increasing of strain rate was expected to be due to structural breakdown of weak bonds that hold particulate matters together [35]. This might lead to the formation of aggregates and reduce apparent viscosity.

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