Mixed Polymeric Micelles for Rapamycin Skin Delivery
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 <spa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/3/569 |
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| author | Guillaume Le Guyader Bernard Do Ivo B. Rietveld Pascale Coric Serge Bouaziz Jean-Michel Guigner Philippe-Henri Secretan Karine Andrieux Muriel Paul |
| author_facet | Guillaume Le Guyader Bernard Do Ivo B. Rietveld Pascale Coric Serge Bouaziz Jean-Michel Guigner Philippe-Henri Secretan Karine Andrieux Muriel Paul |
| author_sort | Guillaume Le Guyader |
| collection | DOAJ |
| description | 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 <span style="font-variant: small-caps;">d</span>-α-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 2–8 °C. In addition, compared to hydroalcoholic gel formulations, the studied system allows for better biodistribution on human skin. |
| first_indexed | 2024-03-09T12:58:43Z |
| format | Article |
| id | doaj.art-51227dd701c843f8b047dc46ce9e5319 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T12:58:43Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-51227dd701c843f8b047dc46ce9e53192023-11-30T21:56:45ZengMDPI AGPharmaceutics1999-49232022-03-0114356910.3390/pharmaceutics14030569Mixed Polymeric Micelles for Rapamycin Skin DeliveryGuillaume Le Guyader0Bernard Do1Ivo B. Rietveld2Pascale Coric3Serge Bouaziz4Jean-Michel Guigner5Philippe-Henri Secretan6Karine Andrieux7Muriel Paul8Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, FranceAssistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, FranceSMS Laboratory (EA 3233), Université de Rouen-Normandie, Place Émile Blondel, 76821 Mont Saint Aignan, FranceUMR 8038 CiTCoM, CNRS, University of Paris, 75006 Paris, FranceUMR 8038 CiTCoM, CNRS, University of Paris, 75006 Paris, FranceInstitut de Minéralogie, de Physique des Matériaux et de Cosmochimie (IMPMC), UMR CNRS 7590, MNHN, IRD UR 206, Université Sorbonne Paris Cité, F-75005 Paris, FranceMatériaux et Santé, Université Paris-Saclay, 92296 Châtenay-Malabry, FranceUMR CNRS 8258—U1267 Inserm, Université de Paris, F-75006 Paris, FranceAssistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, FranceFacial 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 <span style="font-variant: small-caps;">d</span>-α-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 2–8 °C. In addition, compared to hydroalcoholic gel formulations, the studied system allows for better biodistribution on human skin.https://www.mdpi.com/1999-4923/14/3/569rapamycinfacial angiofibromasmixed polymeric micellesmicelle-based hydrogelstabilityskin permeation |
| spellingShingle | Guillaume Le Guyader Bernard Do Ivo B. Rietveld Pascale Coric Serge Bouaziz Jean-Michel Guigner Philippe-Henri Secretan Karine Andrieux Muriel Paul Mixed Polymeric Micelles for Rapamycin Skin Delivery Pharmaceutics rapamycin facial angiofibromas mixed polymeric micelles micelle-based hydrogel stability skin permeation |
| title | Mixed Polymeric Micelles for Rapamycin Skin Delivery |
| title_full | Mixed Polymeric Micelles for Rapamycin Skin Delivery |
| title_fullStr | Mixed Polymeric Micelles for Rapamycin Skin Delivery |
| title_full_unstemmed | Mixed Polymeric Micelles for Rapamycin Skin Delivery |
| title_short | Mixed Polymeric Micelles for Rapamycin Skin Delivery |
| title_sort | mixed polymeric micelles for rapamycin skin delivery |
| topic | rapamycin facial angiofibromas mixed polymeric micelles micelle-based hydrogel stability skin permeation |
| url | https://www.mdpi.com/1999-4923/14/3/569 |
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