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      Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles

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          Atopic dermatitis is a chronic, noncontiguous, and exudative disorder accompanied by perivascular infiltration of immune mediators, including T-helper (Type 1 helper/Type 2 helper) cells, mast cells, and immunoglobulin E. The current study explores the immunomodulatory and histological effects of nanoparticle (NP)-based transcutaneous delivery of hydrocortisone (HC).


          In this study, HC, the least potent topical glucocorticoid, was administered transcutaneously as chitosan NPs. The pharmacological and immunological effects of the NP-based HC delivery on the alleviation of 2,4-dinitrofluorobenzene-induced atopic dermatitis (AD)-like skin lesions were evaluated using the NC/Nga mouse model.


          In vivo Dino-Lite ® microscopic assessment revealed that the NP-based formulation displayed a remarkable ability to reduce the severity of the pathological features of AD (dermatitis index, 3.0). The AD suppressive activity of the NP-based topical formulation was expected owing to the interruption of a series of immunopathological events, including the production of immunoglobulin E, release of histamine, and expression of prostaglandin-E 2 and vascular endothelial growth factor-α in the sera and skin of the tested animals. Analysis of the cytokine expression in AD-like skin lesions further revealed that the NP-based formulation inhibited the pathological expression of interleukin (IL)-4, IL-5, IL-6, IL-13, IL-12p70, interferon-γ, and tumor necrosis factor-α in serum and skin homogenates of NC/Nga mice. Further, our histological findings indicated that the NP-based formulation inhibited fibroblast infiltration and fragmentation of elastic fibers, further supporting the clinical importance of these formulations in maintaining the integrity of elastic connective tissues.


          The current investigation suggests that NP-mediated transcutaneous delivery of HC could be considered an effective therapeutic approach to manage dermatitis.

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          Most cited references 32

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          The development of allergic inflammation.

          Allergic disorders, such as anaphylaxis, hay fever, eczema and asthma, now afflict roughly 25% of people in the developed world. In allergic subjects, persistent or repetitive exposure to allergens, which typically are intrinsically innocuous substances common in the environment, results in chronic allergic inflammation. This in turn produces long-term changes in the structure of the affected organs and substantial abnormalities in their function. It is therefore important to understand the characteristics and consequences of acute and chronic allergic inflammation, and in particular to explore how mast cells can contribute to several features of this maladaptive pattern of immunological reactivity.
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            Mast cells in the development of adaptive immune responses.

            Mast cells are so widely recognized as critical effector cells in allergic disorders and other immunoglobulin E-associated acquired immune responses that it can be difficult to think of them in any other context. However, mast cells also can be important as initiators and effectors of innate immunity. In addition, mast cells that are activated during innate immune responses to pathogens, or in other contexts, can secrete products and have cellular functions with the potential to facilitate the development, amplify the magnitude or regulate the kinetics of adaptive immune responses. Thus, mast cells may influence the development, intensity and duration of adaptive immune responses that contribute to host defense, allergy and autoimmunity, rather than simply functioning as effector cells in these settings.
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              Microneedles for transdermal drug delivery.

              The success of transdermal drug delivery has been severely limited by the inability of most drugs to enter the skin at therapeutically useful rates. Recently, the use of micron-scale needles in increasing skin permeability has been proposed and shown to dramatically increase transdermal delivery, especially for macromolecules. Using the tools of the microelectronics industry, microneedles have been fabricated with a range of sizes, shapes and materials. Most drug delivery studies have emphasized solid microneedles, which have been shown to increase skin permeability to a broad range of molecules and nanoparticles in vitro. In vivo studies have demonstrated delivery of oligonucleotides, reduction of blood glucose level by insulin, and induction of immune responses from protein and DNA vaccines. For these studies, needle arrays have been used to pierce holes into skin to increase transport by diffusion or iontophoresis or as drug carriers that release drug into the skin from a microneedle surface coating. Hollow microneedles have also been developed and shown to microinject insulin to diabetic rats. To address practical applications of microneedles, the ratio of microneedle fracture force to skin insertion force (i.e. margin of safety) was found to be optimal for needles with small tip radius and large wall thickness. Microneedles inserted into the skin of human subjects were reported as painless. Together, these results suggest that microneedles represent a promising technology to deliver therapeutic compounds into the skin for a range of possible applications.

                Author and article information

                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                05 November 2014
                : 9
                : 5143-5156
                [1 ]Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
                [2 ]Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, Selangor, Malaysia
                Author notes
                Correspondence: Haliza Katas, Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur Campus, Jalan Raja Muda Abdul Aziz 50300, Kuala Lumpur, Malaysia, Tel +60 392 897 971, Fax +60 26 893 271, Email haliz12@ 123456hotmail.com
                © 2014 Hussain et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Molecular medicine

                chitosan nanocarrier, elastic fibers, glucocorticoids, topical delivery


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