{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:36:28Z","timestamp":1792452988454,"version":"4.5.0"},"reference-count":187,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Romanian Ministry of Education and Research, CCCDI-UEFISCDI","award":["PN-III-P4-ID-PCE-2020-2177"],"award-info":[{"award-number":["PN-III-P4-ID-PCE-2020-2177"]}]},{"name":"Romanian Ministry of Education and Research, CCCDI-UEFISCDI","award":["PCE 157\/2021"],"award-info":[{"award-number":["PCE 157\/2021"]}]},{"name":"PNCDI III","award":["PN-III-P4-ID-PCE-2020-2177"],"award-info":[{"award-number":["PN-III-P4-ID-PCE-2020-2177"]}]},{"name":"PNCDI III","award":["PCE 157\/2021"],"award-info":[{"award-number":["PCE 157\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Azelaic acid (AzA), a saturated dicarboxylic acid, is indicated for the treatment of acne vulgaris, rosacea, melasma, and post-inflammatory hyperpigmentation. Its antimicrobial, anti-inflammatory, and antimelanogenic properties support its use; however, its poor aqueous solubility and limited skin permeability constrain its optimal topical delivery. This review summarizes clinical evidence and advances in formulations\u2014including conventional vehicles, polymeric\/lipid nanocarriers, and deep eutectic solvent (DES) systems\u2014to promote more effective and well-tolerated use. Across indications, 15\u201320% azelaic acid (AzA) formulations produced clinically meaningful improvements with mild, transient local irritation. For acne vulgaris, reductions in inflammatory and noninflammatory lesions were comparable to those of topical retinoids\/adapalene, and tolerability was superior in some studies. For rosacea, the 15% gel formulation was comparable to metronidazole in reducing papules, pustules, and erythema while maintaining negligible systemic exposure. In melasma and other dyschromias, 20% cream demonstrated efficacy similar to hydroquinone, exhibiting a favorable safety profile. Advanced delivery systems, including liposomes, niosomes\/ethosomes, nanostructured lipid carriers, microemulsions, nanosponges, and DES platforms, increased AzA solubilization, cutaneous deposition, and stability. This enabled dose-sparing strategies and improved adherence. Data on AzA cocrystals and ionic salts suggest additional control over release and irritation. AzA remains a versatile and well-tolerated dermatologic agent whose performance is strongly vehicle-dependent. Rational selection and engineering of carriers, particularly DES-integrated polymeric and lipid systems, can mitigate solubility and permeability limitations, enhance skin targeting, and reduce irritation in the treatment of acne and rosacea.<\/jats:p>","DOI":"10.3390\/ph18091273","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T14:18:49Z","timestamp":1756217929000},"page":"1273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A Comprehensive Review of Azelaic Acid Pharmacological Properties, Clinical Applications, and Innovative Topical Formulations"],"prefix":"10.3390","volume":"18","author":[{"given":"Andreea-Georgiana","family":"Petrovici","sequence":"first","affiliation":[{"name":"Biocatalysis and Green Chemistry Group, Faculty Chemical Engineering, Biotechnologies and Environmental Protection, University Politehnica Timisoara, Vasile P\u00e2rvan 6, 300223 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0908-1196","authenticated-orcid":false,"given":"Mariachiara","family":"Spennato","sequence":"additional","affiliation":[{"name":"Department of Civil, Chemical, Environmental and Materials Engineering, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7609-8735","authenticated-orcid":false,"given":"Ioan","family":"B\u00eetcan","sequence":"additional","affiliation":[{"name":"Biocatalysis and Green Chemistry Group, Faculty Chemical Engineering, Biotechnologies and Environmental Protection, University Politehnica Timisoara, Vasile P\u00e2rvan 6, 300223 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7248-2641","authenticated-orcid":false,"given":"Francisc","family":"P\u00e9ter","sequence":"additional","affiliation":[{"name":"Biocatalysis and Green Chemistry Group, Faculty Chemical Engineering, Biotechnologies and Environmental Protection, University Politehnica Timisoara, Vasile P\u00e2rvan 6, 300223 Timisoara, Romania"},{"name":"Renewable Energy Research Institute-ICER, University Politehnica Timisoara, Gavril Musicescu 138, 300501 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livius","family":"Cotarc\u0103","sequence":"additional","affiliation":[{"name":"LC Consulting SAS, Via Martignacco 117, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7744-103X","authenticated-orcid":false,"given":"Anamaria","family":"Todea","sequence":"additional","affiliation":[{"name":"Biocatalysis and Green Chemistry Group, Faculty Chemical Engineering, Biotechnologies and Environmental Protection, University Politehnica Timisoara, Vasile P\u00e2rvan 6, 300223 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin Lauren\u021biu","family":"Ordodi","sequence":"additional","affiliation":[{"name":"Biocatalysis and Green Chemistry Group, Faculty Chemical Engineering, Biotechnologies and Environmental Protection, University Politehnica Timisoara, Vasile P\u00e2rvan 6, 300223 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1080\/09546634.2020.1800579","article-title":"The versatility of azelaic acid in dermatology","volume":"33","author":"Searle","year":"2022","journal-title":"J. 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