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However, most of these drugs display low water solubility, which makes their incorporation into hydrophilic biopolymeric drug-delivery systems difficult. To overcome this drawback, aqueous solutions of bio-based deep eutectic solvents (DES) were investigated to enhance the solubility of ibuprofen, a widely used NSAID, leading to an increase in its solubility of up to 7917-fold when compared to its water solubility. These DES solutions were shown to be non-toxic to macrophages with cell viabilities of 97.4% (at ibuprofen concentrations of 0.25 mM), while preserving the anti-inflammatory action of the drug. Their incorporation into alginate-based hydrogels resulted in materials with a regular structure and higher flexibility. These hydrogels present a sustained release of the drug, which is able, when containing the DES aqueous solution comprising ibuprofen, to deliver 93.5% of the drug after 8 h in PBS. Furthermore, these hydrogels were able to improve the drug permeation across human skin by 8.5-fold in comparison with the hydrogel counterpart containing only ibuprofen. This work highlights the possibility to remarkably improve the transdermal administration of NSAIDs by combining new drug formulations based on DES and biopolymeric drug delivery systems.<\/jats:p>","DOI":"10.3390\/pharmaceutics14040827","type":"journal-article","created":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T06:02:54Z","timestamp":1649570574000},"page":"827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Deep Eutectic Solvent Formulations and Alginate-Based Hydrogels as a New Partnership for the Transdermal Administration of Anti-Inflammatory Drugs"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9483-0686","authenticated-orcid":false,"given":"S\u00f3nia N.","family":"Pedro","sequence":"first","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6631-9821","authenticated-orcid":false,"given":"Maria S. M.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-3124","authenticated-orcid":false,"given":"Bruno M.","family":"Neves","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-048X","authenticated-orcid":false,"given":"Isabel Filipa","family":"Almeida","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO, Applied Molecular Biosciences Unit, MedTech-Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-3398","authenticated-orcid":false,"given":"Paulo","family":"Costa","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO, Applied Molecular Biosciences Unit, MedTech-Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"In\u00eas","family":"Correia-S\u00e1","sequence":"additional","affiliation":[{"name":"Department of Plastic, Aesthetic, Reconstructive and Aesthetic Surgery, Centro Hospitalar de S. Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9212-2704","authenticated-orcid":false,"given":"Carla","family":"Vilela","sequence":"additional","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8895-0614","authenticated-orcid":false,"given":"Mara G.","family":"Freire","sequence":"additional","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5403-8416","authenticated-orcid":false,"given":"Armando J. D.","family":"Silvestre","sequence":"additional","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-4663","authenticated-orcid":false,"given":"Carmen S. 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