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    ABSTRACT: Abstract This study evaluated the feasibility of mizolastine-loaded microparticles as therapy for atopic dermatitis. Microparticles have been researched for decades as a controlled-release drug delivery system, but seldom been used as treatment for skin disease. In this research, we induced dermatitis in BALB/c mice model by repeated topical application of dinitrofluorobenzene and compared the mizolastine microparticles injection and daily mizolastine injection treatment. The results showed that the mizolastine microparticles treatments significantly inhibited ear thickness and dermatitis index in dermatitis model compared with the dermatitis mice without treatment, showing a similar curative effect compared with daily mizolastine injection treatment, and the improvement continued for several days. Inflammatory cells infiltration into the ears and the plasma level of immunoglobulin E were also suppressed by mizolastine microparticles according to the histopathology analysis. In conclusion, the results suggested that drug-loaded microparticles could be a proper candidate for the treatment of skin diseases.
    Journal of Microencapsulation 12/2014; DOI:10.3109/02652048.2014.995727 · 1.88 Impact Factor
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    ABSTRACT: Derzeit steht für das atopische Ekzem (AE) keine kausale Behandlung zur Verfügung. Neben der Meidung individueller Provokationsfaktoren umfasst die symptomatische Lokaltherapie eine stadiengerechte Anwendung pflegender und rückfettender sowie ggf. antiseptischer und antiinflammatorischer Externa. Die medikamentöse Therapie des schweren AE ist eine besondere Herausforderung. Als immunsuppressives Systemtherapeutikum ist in Deutschland derzeit nur Ciclosporin zugelassen; zur Unterbrechung des akuten Schubes können auch orale Glukokortikosteroide eingesetzt werden. Daneben stellen Methotrexat (MTX), Azathioprin, Mycophenolatmofetil und Leflunomid immunsuppressive Therapieoptionen im Einzelfall dar („off-label use“), die jedoch meist nur in kleineren Fallserien oder unkontrollierten Studien untersucht wurden. Während in den letzten Jahren für die Behandlung der Psoriasis eine Reihe hochwirksamer Biologika entwickelt wurde, gibt es noch kein Medikament aus dieser Gruppe, welches für die Therapie des AE zugelassen ist. In offenen Anwendungsbeobachtungen ergaben sich jedoch Hinweise auf eine Wirksamkeit von Alefacept (Fusionsprotein, Inhibition der T-Zell-Aktivierung), Efalizumab (Anti-LFA-1-Antikörper), Rituximab (Anti-CD-20-Antikörper) und Omalizumab (Anti-IgE-Antikörper) zumindest bei Subgruppen von Patienten. Neben der extrakorporalen Photopherese könnte außerdem die Immunglobulin-Immunadsorption eine Option zur Behandlung des therapierefraktären AE darstellen. Bei Patienten mit klinisch relevanter Sensibilisierung gegenüber Aeroallergenen ist die spezifische Immuntherapie, auch hinsichtlich des AE, durchaus eine Therapieoption. Basierend auf zahlreichen neuen Erkenntnissen zur Pathogenese des AE werden derzeit eine Reihe neuer therapeutischer Ansätze verfolgt. Zielstrukturen sind unter anderem Filaggrinstoffwechsel und epidermale Proteasen, Tachykininrezeptoren, Histaminrezeptor 4, Interleukin-31 und Phosphodiesterase-4. Summary To date, there is no simple cure for atopic eczema (AE). Besides the avoidance of specific and unspecific trigger factors the stepped approach to management includes a basic emollients therapy and, according to the severity of symptoms, the addition of antiseptic and/or anti-inflammatory topical treatments. In cases of moderate to severe AE additional systemic treatment is needed to control the disease. Currently only cyclosporine is approved in Germany; oral corticosteroids can be used for a short time for severe acute exacerbations. Systemic immunosuppression with methotrexate, azathioprine, mycophenolat mofetil and leflunomide may also be used with success (off-label use), but these agents remain to be assessed in larger randomized trials. While in the past years a number of biologicals have been developed for the treatment of psoriasis vulgaris, there is currently no biological approved for the treatment of AE. Preliminary data points towards a potential efficacy of alefacept [fusion protein of lymphocyte function antigen (LFA)-3], efalizumab (anti-CD11a antibody, no longer available), rituximab (anti-CD20 antibody) and omalizumab (anti-IgE-antibody) at least in subgroups of AE patients. Apart from the extracorporeal photopheresis immunoadsorption could be an option for cases resistant to other treatments, but needs to be assessed in more detail. In patients with a clinically relevant sensitization towards aeroallergens specific immunotherapy might be an option. Based on many new insights into the pathogenesis currently a number of new therapeutic approaches are being developed; among others, target structures are filaggrin, epidermal proteases, tachykinine receptors, histamine receptor 4, interleukin 31 and phosphodiesterase 4.
    Allergo Journal: interdisziplinäre Zeitschrift für Allergologie und Umweltmedizin: Organ der Deutschen Gesellschaft für Allergie- und Immunitätsforschung 10/2012; 21(7):404-416. DOI:10.1007/s15007-012-0391-2
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    ABSTRACT: Traditionally, asthma and allergic diseases have been defined by broad definitions and treated with nonspecific medications, including corticosteroids and bronchodilators. There is an increasing appreciation of heterogeneity within asthma and allergic diseases based primarily on recent cluster analyses, molecular phenotyping, biomarkers, and differential responses to targeted and nontargeted therapies. These pioneering studies have led to successful therapeutic trials of molecularly targeted therapies in defined phenotypes. This review analyzed randomized double-blind, placebo-controlled trials of molecularly targeted therapies in defined allergic disease and asthma phenotypes. IgE was the first successful biological target used in patients with allergic disease and asthma. This review shows that therapies targeting the canonical type 2 cytokines IL-4, IL-5, and IL-13 have shown consistent efficacy, especially in asthmatic patients with evidence of TH2/type 2 inflammation ("type 2 high"). As of yet, there are no successful trials of targeted therapies in asthmatic patients without evidence for type 2 inflammation. We conclude that further refinement of type 2 therapies to specific type 2 phenotypes and novel approaches for patients without type 2 inflammation are needed for asthma and allergic disease treatment. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    Journal of Allergy and Clinical Immunology 02/2015; 135(2):299-310. DOI:10.1016/j.jaci.2014.12.1871 · 11.25 Impact Factor