{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:44:18Z","timestamp":1790948658034,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"crossref","award":["PNURSP2026R141"],"award-info":[{"award-number":["PNURSP2026R141"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Aspasomes (ASPs) are composed of ascorbyl palmitate (AP), which has antioxidant activity. The objective of this study was the formulation of aspasomes (ASPs) loaded with metformin hydrochloride (MFC) for the topical treatment of melasma. Methods: MFC-ASPs were prepared using the thin-film method with different amounts of phospholipid and ascorbyl palmitate (AP) in the absence or presence of ethanol surfactant. The prepared formulations were optimized using a D-optimal mixture. The assessed responses included entrapment efficiency (%EE), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). Results: The optimum OASPs, composed of 193.121 mg PC and 30 mg AP, exhibited spherical vesicles with an EE% of 87.50 \u00b1 0.33%, PS of 264.47 \u00b1 0.02 nm, PDI of 0.423 \u00b1 0.001, and ZP of \u221221.67 \u00b1 0.12 mV. The optimum formula represented a spherical morphology using transmission electron microscopy, along with sustained release behavior compared with MFC. Also, it showed good stability for up to 90 days. Furthermore, a clinical appraisal of patients with melasma confirmed the superiority of the cream compared to the other cream in clinical study. Conclusions: The optimum OASPs present a promising approach for the treatment of melasma topically.<\/jats:p>","DOI":"10.3390\/pharmaceutics18030364","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:13:14Z","timestamp":1773659594000},"page":"364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Innovative Nanocarriers: Elastic Aspasomes Loaded with Metformin Hydrochloride for Effective Management of Melasma: In Vitro Studies and Clinical Appraisal"],"prefix":"10.3390","volume":"18","author":[{"given":"Rofida","family":"Albash","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza 12568, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdurrahman M.","family":"Fahmy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 12613, Egypt"},{"name":"School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo 11865, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha H.","family":"Ragaie","sequence":"additional","affiliation":[{"name":"Department of Dermatology, STD\u2019s and Andrology, Faculty of Medicine, Minia University, Al-Minya 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimaa S.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Dermatology, STD\u2019s and Andrology, Faculty of Medicine, Minia University, Al-Minya 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4728-5723","authenticated-orcid":false,"given":"Rabab A.","family":"El-Gazar","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, October 6 University, Giza 12585, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-6036","authenticated-orcid":false,"given":"Amira B.","family":"Kassem","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour 22514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8273-2923","authenticated-orcid":false,"given":"Manar Adel","family":"Abdelbari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6089-6062","authenticated-orcid":false,"given":"Hoda A.","family":"Salem","sequence":"additional","affiliation":[{"name":"Pharmacy Practice Department, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-319X","authenticated-orcid":false,"given":"Asmaa","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa","family":"Mosallam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1111\/ijd.17718","article-title":"Pathogenesis of Melasma Explained","volume":"64","author":"Ali","year":"2025","journal-title":"Int. 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