Coencapsulation of Immunosuppressive Drug with Anti-Inflammatory Molecule in Pickering Emulsions as an Innovative Therapeutic Approach for Inflammatory Dermatoses

Maxime Sintès , Petra Kovjenic , Liasmine Haine (Hablal) , Kevin Serror , Mohamed Beladjine , Véronique Parietti (Montcuquet) , Marine Delagrange , Bertrand Ducos , Jean-David Bouaziz , David Boccara , Maurice Mimoun , Armand Bensussan , Martine Bagot , Nicolas Huang , Laurence Michel
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Abstract

Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and burning sensation, leading to poor patient adherence. To overcome these downsides, pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A– or tacrolimus-loaded poly(lactic-co-glycolic) acid nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induced psoriasis-like mouse model. Results showed that both emulsions significantly inhibited nuclear factor of activated T cell translocation in T lymphocytes as well as their IL-2 production, cell activation, and proliferation. In keratinocytes, inhibition of nuclear factor of activated T cell translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivo showed accumulation of rhodamin B–coupled poly(lactic-co-glycolic) acid nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation to a reduced expression of activation markers CD40, CD86, and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T-cell markers, proinflammatory cytokines, chemokines, and specific epidermal cell genes. Altogether, pickering emulsion might be a very efficient formulation for treating inflammatory dermatoses.

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"皮克林乳剂中免疫抑制药物与消炎分子的共包囊是治疗炎症性皮肤病的新方法
银屑病是一种以表皮和免疫功能失调为特征的炎症性皮肤病。目前的外用疗法虽然有效,但会产生不良反应,包括皮肤萎缩和灼烧感,导致患者依从性差。为了克服这些弊端,研究人员配制了皮克乳剂,其中含有钙三醇的分散相由环孢素 A 或他克莫司负载的聚(乳酸-共-乙醇)酸纳米粒子稳定。本研究旨在探讨它们对淋巴细胞和表皮细胞的生物效应,以及在咪喹莫特诱导的类银屑病小鼠模型中的有效性。结果表明,这两种乳剂都能明显抑制活化 T 细胞核因子在 T 淋巴细胞中的转位,以及它们的 IL-2 生成、细胞活化和增殖。在角质细胞中,抑制活化 T 细胞核因子转位可减少 IL-8 和 TNF-α 的产生。在体外皮肤活检组织上局部涂抹乳剂后,免疫荧光显示整个表皮中积累了罗丹明 B 偶联聚(乳酸-共聚乙醇)酸纳米粒子,并显著降低了朗格汉斯细胞的抗原呈递能力,这与活化标记 CD40、CD86 和 HLA-DR 的表达减少有关。通过使用咪喹莫特诱导的体内银屑病模型,泡腾乳液明显减轻了银屑病皮损,这可能是由于皮肤上的 T 细胞标志物、促炎细胞因子、趋化因子和特定表皮细胞基因的表达减少所致。总之,酸模乳剂可能是治疗炎症性皮肤病的一种非常有效的配方。
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Cover 1 Corrigendum to ‘Proteomic Profiling of CCCA Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation’ JID Innovations, Volume 4, Issue 3, May 2024, 100263 Identification of Associations with Dermatologic Diseases through a Focused GWAS of the UK Biobank From Plant to Patient: A Historical Perspective and Review of Selected Medicinal Plants in Dermatology Spatial Transcriptomics in Inflammatory Skin Diseases Using GeoMx Digital Spatial Profiling: A Practical Guide for Applications in Dermatology
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