{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:45:30Z","timestamp":1791935130789,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Facial angiofibromas (FA) are one of the most obvious cutaneous manifestations of tuberous sclerosis complex. Topical rapamycin for angiofibromas has been reported as a promising treatment. Several types of vehicles have been used hitherto, but polymeric micelles and especially those made of d-\u03b1-tocopherol polyethylene glycol 1000 succinate (TPGS) seem to have shown better skin bioavailability of rapamycin than the so far commonly used ointments. To better understand the influence of polymeric micelles on the behavior of rapamycin, we explored it through mixed polymeric micelles combining TPGS and poloxamer, evaluating stability and skin bioavailability to define an optimized formulation to effectively treat FA. Our studies have shown that TPGS improves the physicochemical behavior of rapamycin, i.e., its solubility and stability, due to a strong inclusion in micelles, while poloxamer P123 has a more significant influence on skin bioavailability. Accordingly, we formulated mixed-micelle hydrogels containing 0.1% rapamycin, and the optimized formulation was found to be stable for up to 3 months at 2\u20138 \u00b0C. In addition, compared to hydroalcoholic gel formulations, the studied system allows for better biodistribution on human skin.<\/jats:p>","DOI":"10.3390\/pharmaceutics14030569","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:40:02Z","timestamp":1646599202000},"page":"569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Mixed Polymeric Micelles for Rapamycin Skin Delivery"],"prefix":"10.3390","volume":"14","author":[{"given":"Guillaume","family":"Le Guyader","sequence":"first","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pitaux Universitaires Henri Mondor, F-94010 Cr\u00e9teil, France"},{"name":"Centre Hospitalier Intercommunal de Cr\u00e9teil, F-94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1131-2080","authenticated-orcid":false,"given":"Bernard","family":"Do","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pitaux Universitaires Henri Mondor, F-94010 Cr\u00e9teil, France"},{"name":"Mat\u00e9riaux et Sant\u00e9, Universit\u00e9 Paris-Saclay, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-3998","authenticated-orcid":false,"given":"Ivo B.","family":"Rietveld","sequence":"additional","affiliation":[{"name":"SMS Laboratory (EA 3233), Universit\u00e9 de Rouen-Normandie, Place \u00c9mile Blondel, 76821 Mont Saint Aignan, France"},{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 de Paris, 4 Avenue de l\u2019Observatoire, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8484-1381","authenticated-orcid":false,"given":"Pascale","family":"Coric","sequence":"additional","affiliation":[{"name":"UMR 8038 CiTCoM, CNRS, University of Paris, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7792-8307","authenticated-orcid":false,"given":"Serge","family":"Bouaziz","sequence":"additional","affiliation":[{"name":"UMR 8038 CiTCoM, CNRS, University of Paris, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Guigner","sequence":"additional","affiliation":[{"name":"Institut de Min\u00e9ralogie, de Physique des Mat\u00e9riaux et de Cosmochimie (IMPMC), UMR CNRS 7590, MNHN, IRD UR 206, Universit\u00e9 Sorbonne Paris Cit\u00e9, F-75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-3695","authenticated-orcid":false,"given":"Philippe-Henri","family":"Secretan","sequence":"additional","affiliation":[{"name":"Mat\u00e9riaux et Sant\u00e9, Universit\u00e9 Paris-Saclay, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2002-7556","authenticated-orcid":false,"given":"Karine","family":"Andrieux","sequence":"additional","affiliation":[{"name":"UMR CNRS 8258\u2014U1267 Inserm, Universit\u00e9 de Paris, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Paul","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pitaux Universitaires Henri Mondor, F-94010 Cr\u00e9teil, France"},{"name":"EpidermE, Universit\u00e9 Paris Est Cr\u00e9teil, F-94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1749-6632.2009.05117.x","article-title":"The tuberous sclerosis complex","volume":"1184","author":"Orlova","year":"2010","journal-title":"Ann. 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