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In order to improve the effectiveness of treatment, not only are new active substances with antifungal activity synthesized, but new, unconventional carriers are also developed for substances already used. Methods: Therefore, the focus of this research was to evaluate the possibility of using a combination of two cross-linking techniques for sodium alginate ionic cross-linking with Zn2+ ions and electrostatic interaction with \u03b5-poly-L-lysine. The pharmaceutical properties, antifungal activity against Candida strains, and compatibility with human fibroblasts of the designed hydrogels were assessed. Results: It was shown that the double cross-linking process increased the viscosity of the developed hydrogels, improved bioadhesive properties to hairless mice skin, and provided an extended release profile of the active substance. In addition, obtained formulations were characterized by improved antifungal effect against C. albicans, C. krusei, and C. parapsilosis. Prepared hydrogels expressed biocompatibility with human fibroblasts. Conclusions: Dual-cross-linked alginate hydrogels are a promising dermatological formulation that might improve the efficacy of posaconazole in the treatment of antifungal infections.<\/jats:p>","DOI":"10.3390\/pharmaceutics17081055","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T14:51:46Z","timestamp":1755183106000},"page":"1055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dual-Cross-Linked Alginate Hydrogels as a Strategy to Improve the Antifungal Properties of Posaconazole"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8528-3764","authenticated-orcid":false,"given":"Katarzyna","family":"Sosnowska","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Medical University of Bia\u0142ystok, Mickiewicza 2C, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4340-5350","authenticated-orcid":false,"given":"Marta","family":"Szekalska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Medical University of Bia\u0142ystok, Mickiewicza 2C, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Piktel","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Nanomedicine, Medical University of Bia\u0142ystok, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7664-9226","authenticated-orcid":false,"given":"Robert","family":"Bucki","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bia\u0142ystok, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza","family":"Wolska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Medical University of Gda\u0144sk, Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6191-6053","authenticated-orcid":false,"given":"Iwona","family":"Misztalewska-Turkowicz","sequence":"additional","affiliation":[{"name":"Department of Polymers and Organic Synthesis, Faculty of Chemistry, University of Bia\u0142ystok, Cio\u0142kowskiego 1K, 15-245 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-0489","authenticated-orcid":false,"given":"Karolina Halina","family":"Markiewicz","sequence":"additional","affiliation":[{"name":"Department of Polymers and Organic Synthesis, Faculty of Chemistry, University of Bia\u0142ystok, Cio\u0142kowskiego 1K, 15-245 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka Zofia","family":"Wilczewska","sequence":"additional","affiliation":[{"name":"Department of Polymers and Organic Synthesis, Faculty of Chemistry, University of Bia\u0142ystok, Cio\u0142kowskiego 1K, 15-245 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1013-610X","authenticated-orcid":false,"given":"Katarzyna","family":"Winnicka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Medical University of Bia\u0142ystok, Mickiewicza 2C, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Almoshari, Y. 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