{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T02:18:02Z","timestamp":1775787482098,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"Compete 2020, Portugal 2020 and the European Union","doi-asserted-by":"publisher","award":["POCI\u221201\u22120247\u2212FEDER\u2212027578"],"award-info":[{"award-number":["POCI\u221201\u22120247\u2212FEDER\u2212027578"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The encapsulation of retinol within silica microparticles has emerged as a promising opportunity in the realm of cosmetic and pharmaceutical formulations, driven by the need to reinforce the photoprotection and oxidation stability of retinol. This work examines the process of encapsulating retinol into silica microparticles. The association efficiency, microparticle size, molecular structure, morphology, oxidation, and release profile, as well as biocompatibility and skin sensitization, were evaluated. Results showed that 0.03% of retinol and 9% of emulsifier leads to an association efficiency higher than 99% and a particle size with an average of 5.2 \u00b5m. FTIR results indicate that there is an association of retinol with the silica microparticles, and some may be on the surface. Microscopy indicates that when association happens, there is less aggregation of the particles. Oxidation occurs in two different phases, the first related to the retinol on the surface and the second to the associated retinol. In addition, a burst release of up to 3 h (30% free retinol, 17% associated retinol) was observed, as well as a sustained release of 44% of retinol up to 24 h. Encapsulation allowed an increase in the minimal skin cytotoxic concentrations of retinol from 0.04 \u03bcg\/mL to 1.25 mg\/mL without skin sensitization. Overall, retinol is protected when associated with silica microparticles, being safe to use in cosmetics and dermatology.<\/jats:p>","DOI":"10.3390\/ijms25063215","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T03:55:34Z","timestamp":1710215734000},"page":"3215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Silica Microparticles from Sugarcane By-Products as an Encapsulation System for Retinoids Aimed at Topical Sustained Release"],"prefix":"10.3390","volume":"25","author":[{"given":"Joana R.","family":"Costa","sequence":"first","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2013Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, Rua de Diogo Botelho 1327, 4169-005 Porto, Portugal"}]},{"given":"Ana Helena","family":"Costa","sequence":"additional","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2013Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, Rua de Diogo Botelho 1327, 4169-005 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1754-9254","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Azevedo-Silva","sequence":"additional","affiliation":[{"name":"Amyris Bio Products Portugal, Rua de Diogo Botelho 1327, 4169-005 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9367-5979","authenticated-orcid":false,"given":"Diana","family":"Tavares-Valente","sequence":"additional","affiliation":[{"name":"Amyris Bio Products Portugal, Rua de Diogo Botelho 1327, 4169-005 Porto, Portugal"}]},{"given":"S\u00e9rgio C.","family":"Sousa","sequence":"additional","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2013Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, Rua de Diogo Botelho 1327, 4169-005 Porto, Portugal"}]},{"given":"T\u00e2nia","family":"Neto","sequence":"additional","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2013Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, Rua de Diogo Botelho 1327, 4169-005 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0760-3184","authenticated-orcid":false,"given":"Manuela E.","family":"Pintado","sequence":"additional","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2013Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, Rua de Diogo Botelho 1327, 4169-005 Porto, Portugal"}]},{"given":"Ana Raquel","family":"Madureira","sequence":"additional","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2013Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, Rua de Diogo Botelho 1327, 4169-005 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s13671-015-0102-9","article-title":"Topical retinoids and Cosmeceuticals: Where is the scientific evidence to recommend products to patients?","volume":"4","author":"Higgins","year":"2015","journal-title":"Curr. Dermatol. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"392","DOI":"10.5114\/ada.2019.87443","article-title":"Retinoids: Active molecules influencing skin structure formation in cosmetic and dermatological treatments","volume":"36","author":"Zasada","year":"2019","journal-title":"Postep. Dermatol. Alergol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2147\/ciia.2006.1.4.327","article-title":"Retinoids in the treatment of skin aging: An overview of clinical efficacy and safety","volume":"1","author":"Mukherjee","year":"2006","journal-title":"Clin. Interv. Aging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1177\/12034754211035091","article-title":"A Clinician\u2019s Guide to Topical Retinoids","volume":"26","author":"Motamedi","year":"2022","journal-title":"J. Cutan Med. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/379335a0","article-title":"Molecular basis of sun-induced premature skin ageing and retinoid antagonism","volume":"379","author":"Fisher","year":"1996","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.1038\/s41467-020-18042-2","article-title":"Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine","volume":"11","author":"Ferreira","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ijpharm.2013.08.019","article-title":"Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption, photostability, biocompatibility and anti-psoriatic activity","volume":"456","author":"Raza","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106458","DOI":"10.1016\/j.ejps.2023.106458","article-title":"Lipid-based nanoformulation optimization for achieving cutaneous targeting: Niosomes as the potential candidates to fulfill this aim","volume":"186","author":"Lin","year":"2023","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"446","DOI":"10.34172\/apb.2023.056","article-title":"An Overview of Nanostructured Lipid Carriers and its Application in Drug Delivery through Different Routes","volume":"13","author":"Khan","year":"2023","journal-title":"Adv. Pharm. Bull."},{"key":"ref_10","first-page":"37","article-title":"All-trans retinoic acid solid lipid nanoparticle characterisation and assessment of anti-inflammatory activity in a human lung epithelial cell line","volume":"1","author":"Millar","year":"2017","journal-title":"RCSI Med. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.colsurfb.2011.07.036","article-title":"Formulation design, preparation and physicochemical characterizations of solid lipid nanoparticles containing a hydrophobic drug: Effects of process variables","volume":"88","author":"Das","year":"2011","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jconrel.2004.11.020","article-title":"Liposomes as carriers for dermal delivery of tretinoin: In vitro evaluation of drug permeation and vesicle\u2013skin interaction","volume":"103","author":"Sinico","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ijpharm.2014.10.031","article-title":"Development of novel diolein\u2013niosomes for cutaneous delivery of tretinoin: Influence of formulation and in vitro assessment","volume":"477","author":"Manca","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, H., Hu, Y., Jeong, D., Jun, B.H., Cho, E., and Jung, S. (2016). Synthesis, Characterization, and Retinol Stabilization of Fatty Amide-\u03b2-cyclodextrin Conjugates. Molecules, 21.","DOI":"10.3390\/molecules21070963"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zuccari, G., Baldassari, S., Alfei, S., Marengo, B., Valenti, G.E., Domenicotti, C., Ailuno, G., Villa, C., Marchitto, L., and Caviglioli, G. (2021). D-\u03b1-Tocopherol-Based Micelles for Successful Encapsulation of Retinoic Acid. Pharmaceuticals, 14.","DOI":"10.3390\/ph14030212"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/japtr.JAPTR_314_17","article-title":"Polymeric micelles as cutaneous drug delivery system in normal skin and dermatological disorders","volume":"9","author":"Chavoshy","year":"2018","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jconrel.2018.03.023","article-title":"Encapsulation and controlled release of retinol from silicone particles for topical delivery","volume":"278","author":"Shields","year":"2018","journal-title":"J. Control. Release."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121439","DOI":"10.1016\/j.ijpharm.2021.121439","article-title":"Skin interaction, permeation and toxicity of silica nanoparticles: Challenges and recent therapeutic and cosmetic advances","volume":"614","author":"Morais","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1006\/jcis.2001.7699","article-title":"Preparation of Silica Particles Encapsulating Retinol Using O\/W\/O Multiple Emulsions","volume":"240","author":"Lee","year":"2001","journal-title":"J. Colloid Interface Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5351","DOI":"10.1007\/s12325-022-02319-7","article-title":"Use of Retinoids in Topical Antiaging Treatments: A Focused Review of Clinical Evidence for Conventional and Nanoformulations","volume":"3","author":"Milosheska","year":"2022","journal-title":"Adv. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Costa, J.R., Capeto, A.P., Pereira, C.F., Pedrosa, S.S., Mota, I.F., Burgal, J.d.S., Pintado, A.I., Pintado, M.E., Oliveira, C.S.S., and Costa, P. (2022). Valorization of Sugarcane By-Products through Synthesis of Biogenic Amorphous Silica Microspheres for Sustainable Cosmetics. Nanomater, 12.","DOI":"10.3390\/nano12234201"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.foodchem.2014.12.015","article-title":"Vitamin A Palmitate-\u03b2-cyclodextrin inclusion complexes: Characterization, protection and emulsification properties","volume":"175","author":"Vilanova","year":"2015","journal-title":"Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mujica-\u00c1lvarez, J., Gil-Castell, O., Barra, P.A., Ribes-Greus, A., Bustos, R., Faccini, M., and Matiacevich, S. (2020). Encapsulation of Vitamins A and E as Spray-Dried Additives for the Feed Industry. Molecules, 25.","DOI":"10.3390\/molecules25061357"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kim, S.-H., Lee, D.H., Choi, S., Yang, J.-Y., Jung, K., Jeong, J., Oh, J.H., and Lee, J.H. (2021). Skin Sensitization Potential and Cellular ROS-Induced Cytotoxicity of Silica Nanoparticles. Nanomater, 11.","DOI":"10.3390\/nano11082140"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0301-4622(98)00158-6","article-title":"Liposome encapsulated vitamin A compounds exhibit greater stability and diminished toxicity","volume":"73","author":"Singh","year":"1998","journal-title":"Biophys. Chem."},{"key":"ref_26","unstructured":"Organisation for Economic Cooperation and Development (2024, March 08). Test Guideline No. 442C\u2013In Chemico Skin Sensitisation. Assays Addressing the Adverse Outcome Pathway Key Event on Covalent Binding to Proteins. Available online: https:\/\/www.oecd-ilibrary.org\/environment\/test-no-442c-in-chemico-skin-sensitisation_9789264229709-en."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Goudon, F., Cl\u00e9ment, Y., and Ripoll, L. (2020). Controlled Release of Retinol in Cationic Co-Polymeric Nanoparticles for Topical Application. Cosmetics, 7.","DOI":"10.3390\/cosmetics7020029"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"113305","DOI":"10.1016\/j.colsurfb.2023.113305","article-title":"Biogenic silica microparticles as a new and sustainable cosmetic ingredient: Assessment of performance and quality parameters","volume":"226","author":"Costa","year":"2023","journal-title":"Colloids Surf. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ijpharm.2009.07.025","article-title":"Formation of ion pairing as an alternative to improve encapsulation and stability and to reduce skin irritation of retinoic acid loaded in solid lipid nanoparticles","volume":"381","author":"Castro","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_30","unstructured":"(2023). Reference Test Method for Release of Nickel from All Post Assemblies Which Are Inserted into Pierced Parts of the Human Body and Articles Intended to Come into Direct and Prolonged Contact with the Skin (Standard No. DIN Standard EN 1811)."},{"key":"ref_31","unstructured":"(2009). Biological Evaluation of Medical Devices Part 5: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5:2009)."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3215\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:12:16Z","timestamp":1760105536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,12]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25063215"],"URL":"https:\/\/doi.org\/10.3390\/ijms25063215","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,12]]}}}