Citation: Ben David, N.; Richtman, Y.; Gross, A.; Ibrahim, R.; Nyska, A.; Ramot, Y.; Mizrahi, B. Design and Evaluation of Dissolvable Microneedles for Treating Atopic Dermatitis. Pharmaceutics 2023, 15, 1109. https://doi.org/10.3390/ pharmaceutics15041109 Academic Editors: Salette Reis, Sofia Lima and Tânia Moniz Received: 23 February 2023 Revised: 25 March 2023 Accepted: 28 March 2023 Published: 31 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). pharmaceutics Article Design and Evaluation of Dissolvable Microneedles for Treating Atopic Dermatitis Noa Ben David 1 , Yuval Richtman 1 , Adi Gross 1 , Ruba Ibrahim 2,3 , Abraham Nyska 4 , Yuval Ramot 2,3, * and Boaz Mizrahi 1, * 1 Faculty of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel 2 Department of Dermatology, Hadassah Medical Center, Jerusalem 9112001, Israel 3 Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel 4 Sackler School of Medicine, Tel Aviv University, Tel Aviv 6200515, Israel * Correspondence: yramot@gmail.com (Y.R.); bmizrahi@technion.ac.il (B.M.) Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease caused predominantly by immune dysregulation. The global impact of AD continues to increase, making it not only a significant public health issue but also a risk factor for progression into other allergic phenotype disorders. Treatment of moderate-to-severe symptomatic AD involves general skin care, restoration of the skin barrier function, and local anti-inflammatory drug combinations, and may also require systemic therapy, which is often associated with severe adverse effects and is occasionally unsuitable for long-term use. The main objective of this study was to develop a new delivery system for AD treatment based on dissolvable microneedles containing dexamethasone incorporated in a dissolvable polyvinyl alcohol/polyvinylpyrrolidone matrix. SEM imaging of the microneedles showed well- structured arrays comprising pyramidal needles, fast drug release in vitro in Franz diffusion cells, an appropriate mechanical strength recorded with a texture analyzer, and low cytotoxicity. Significant clinical improvements, including in the dermatitis score, spleen weights, and clinical scores, were observed in an AD in vivo model using BALB/c nude mice. Taken together, our results support the hypothesis that microneedle devices loaded with dexamethasone have great potential as a treatment for AD and possibly for other skin conditions as well. Keywords: dissolving microneedles; atopic dermatitis; drug release; dexamethasone; PVA; PVP 1. Introduction Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction, erythema, edema formation, dryness, and pruritus [1,2] and associated with infiltration of inflammatory mediators such as eosinophils, neutrophils, and mast cells [3]. AD, which affects up to 20% of children and 7% of adults, places a substantial physical, emotional, and financial burden on patients and their families [4]. Treatment of AD aims to reduce the frequency, duration, and severity of symptoms, and is applied in a step- wise manner [5]. Patients with a genetic tendency to develop AD are advised on basic skin care regimens, including liberal and frequent use of moisturizers [6]. Treating moderate- to-severe AD involves restoration of the skin barrier function and drug combinations that suppress local inflammation and prevent local or systemic superinfection [7]. Although topical corticosteroids are considered as the first line of pharmacological treatment, there is a subgroup of patients whose AD does not improve despite increasing applications of topical steroids [8]. In moderate-to-severe disease, systemic immunosuppressants, with or without systemic steroids, are often prescribed. These treatments may be beneficial for many of the patients; however, they might be associated with severe adverse effects, require careful monitoring, and some of them are not suitable for long-term use (e.g., cyclosporine) [7]. More effective and well-tolerated therapies for AD are therefore required [9]. Pharmaceutics 2023, 15, 1109. https://doi.org/10.3390/pharmaceutics15041109 https://www.mdpi.com/journal/pharmaceutics