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However, the low bioavailability and short half\u2010life of the oral pills and the invasiveness of the parenteral injections make these suboptimal therapeutic options. Microneedles, bridging the advantages of the former forms, are successfully used to deliver methotrexate for different therapeutic purposes. However, the utilized dissolving microneedles demand frequent administration, potentially compromising patients\u2019 compliance. Additionally, the high toxicity of methotrexate prompts a quest for safer alternatives. Phloretin, a natural compound with confirmed antipsoriatic potential, emerges as a promising candidate. Herein, microneedle patches with separable, slow\u2010degrading tips are developed for the sustained delivery of methotrexate and phloretin, as a comprehensive solution for long\u2010term psoriasis management. Both compounds are individually loaded at varying doses and display sustained\u2010release profiles. The developed microneedle patches demonstrate high mechanical strength, favorable drug delivery efficiency, and remarkable antipsoriatic potential both in vitro in keratinocytes and in vivo in a psoriasis mouse model. Comparative analysis with two subcutaneous injections reveals a similar antipsoriatic efficacy with a single patch of either compound, with prominent phloretin safety. Therefore, the developed patches present a superior alternative to methotrexate's current marketed forms and provide a viable alternative (phloretin) with comparable antipsoriatic efficacy and higher safety.<\/jats:p>","DOI":"10.1002\/smll.202405927","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T02:06:36Z","timestamp":1728353196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Microneedles with Implantable Tip\u2010Accumulated Therapeutics for the Long\u2010Term Management of Psoriasis"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-9730","authenticated-orcid":false,"given":"Fatma","family":"Moawad","sequence":"first","affiliation":[{"name":"Facult\u00e9 de Pharmacie Universit\u00e9 de Montr\u00e9al  2940 Chemin de Polytechnique Montr\u00e9al Qu\u00e9bec H3T 1J4 Canada"},{"name":"Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef 625617 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Ruel","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie Universit\u00e9 Laval  Qu\u00e9bec Qu\u00e9bec G1V 0A6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nastaran","family":"Rezaei","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie Universit\u00e9 de Montr\u00e9al  2940 Chemin de Polytechnique Montr\u00e9al Qu\u00e9bec H3T 1J4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Alsarraf","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Sciences Fondamentales Centre de Recherche sur la bor\u00e9alie (CREB) Universit\u00e9 du Qu\u00e9bec \u00e0 Chicoutimi  Chicoutimi Qu\u00e9bec G7H 2B1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Pichette","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Sciences Fondamentales Centre de Recherche sur la bor\u00e9alie (CREB) Universit\u00e9 du Qu\u00e9bec \u00e0 Chicoutimi  Chicoutimi Qu\u00e9bec G7H 2B1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Legault","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Sciences Fondamentales Centre de Recherche sur la bor\u00e9alie (CREB) Universit\u00e9 du Qu\u00e9bec \u00e0 Chicoutimi  Chicoutimi Qu\u00e9bec G7H 2B1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxane","family":"Pouliot","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie Universit\u00e9 Laval  Qu\u00e9bec Qu\u00e9bec G1V 0A6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-1125","authenticated-orcid":false,"given":"Davide","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie Universit\u00e9 de Montr\u00e9al  2940 Chemin de Polytechnique Montr\u00e9al Qu\u00e9bec H3T 1J4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,7]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61128-3"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.82"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61129-5"},{"key":"e_1_2_10_3_1","volume":"179","author":"Chen Z.","year":"2018","journal-title":"Br. 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