{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:11:34Z","timestamp":1777468294104,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2019\/16169-0"],"award-info":[{"award-number":["2019\/16169-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04567\/2020 and UIDP\/04567\/2020"],"award-info":[{"award-number":["UIDB\/04567\/2020 and UIDP\/04567\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["305250\/2019-1"],"award-info":[{"award-number":["305250\/2019-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cosmetics"],"abstract":"<jats:p>Progressively growing diagnoses of skin cancer trigger public health concerns about excessive sun exposure, awareness of the deleterious effects of ultraviolet (UV) radiation on the skin, and the proper use of sunscreens. Studies show that bioactive molecules, such as rosmarinic acid (RA), may potentiate the photoprotective and antioxidant activity of topical formulations. This research presents the application of the concepts of quality by design (QbD) to evaluate the critical parameters of quality and the development of an optimized cosmetic formulation with RA by means of an understanding of product design space. Samples were developed using design of experiments (DoE) and they were evaluated for in vitro antioxidant activity and photoprotective efficacy, as well as for photostability through artificial irradiation. We were able to achieve the RA performance regarding antioxidant and SPF properties through in vitro experiments. We obtained the equations for predicting the in vitro antioxidant activity and SPF. Considering our sunscreen system, developed with octyl p-methoxycinnamate and bemotrizinol, the presence of RA increased its antioxidant capacity; however, the in vitro SPF was reduced when both UV filters were used. The development of multifunctional sunscreens is of utmost importance; moreover, there is a need for the rational development of formulations that ensure representative statistical tests of the effects and interactions among the components of a formulation on the desired critical quality attributes, including efficacy.<\/jats:p>","DOI":"10.3390\/cosmetics9020029","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T20:09:57Z","timestamp":1646078997000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Prospecting In Vitro Antioxidant and Photoprotective Properties of Rosmarinic Acid in a Sunscreen System Developed by QbD Containing Octyl p-Methoxycinnamate and Bemotrizinol"],"prefix":"10.3390","volume":"9","author":[{"given":"Thalita Marc\u00edlio","family":"C\u00e2ndido","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, Sao Paulo 05508-000, Brazil"}]},{"given":"Ma\u00edra Bueno","family":"Ariede","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, Sao Paulo 05508-000, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0066-1840","authenticated-orcid":false,"given":"Claudin\u00e9ia Aparecida Sales de Oliveira","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, Sao Paulo 05508-000, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2630-151X","authenticated-orcid":false,"given":"Felipe Rebello","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, Sao Paulo 05508-000, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-6213","authenticated-orcid":false,"given":"Catarina","family":"Rosado","sequence":"additional","affiliation":[{"name":"CBIOS-Research Center for Biosciences and Health Technologies, Universidade Lus\u00f3fona, 1749-024 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4950-8510","authenticated-orcid":false,"given":"Maria Val\u00e9ria Robles","family":"Velasco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, Sao Paulo 05508-000, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9197-3024","authenticated-orcid":false,"given":"Andr\u00e9 Rolim","family":"Baby","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, Sao Paulo 05508-000, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/j.1600-0781.2011.00557.x","article-title":"Current sunscreen controversies: A critical review","volume":"27","author":"Burnett","year":"2011","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1468-2494.2011.00654.x","article-title":"Review of sunscreen and the emergence of non-conventional absorbers and their applications in ultraviolet protection","volume":"33","author":"Morabito","year":"2011","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_3","first-page":"71","article-title":"Sunscreens, Skin Photobiology, and Skin Cancer: The Need for UVA Protection and Evaluation of Efficacy","volume":"108","author":"Gasparro","year":"2000","journal-title":"Environ. Health Perspect."},{"key":"ref_4","first-page":"1","article-title":"Protetores solares e os efeitos da radia\u00e7\u00e3o ultravioleta","volume":"4","author":"Araujo","year":"2008","journal-title":"Sci. Plena"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1590\/S1413-81232008000400030","article-title":"Skin cancer: Use of preventive measures and demographic profile of a risk group in the city of Botucatu","volume":"13","author":"Popim","year":"2004","journal-title":"Cienc. Saude Coletiva"},{"key":"ref_6","unstructured":"Food and Drug Administration (2011). Labeling and Effectiveness Testing; Sunscreen Drug Products for over-the-Conter Human Use."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/j.1529-8019.2007.00150.x","article-title":"Update on photoprotection","volume":"20","author":"Palm","year":"2007","journal-title":"Dermatol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S160","DOI":"10.1016\/j.jaad.2007.04.036","article-title":"The benefit of daily photoprotection","volume":"58","author":"Fourtanier","year":"2008","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ijpharm.2008.06.031","article-title":"Broad spectrum bioactive sunscreens","volume":"363","author":"Velasco","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4062\/biomolther.2015.069","article-title":"Rosmarinic acid attenuates cell damage against UVB radiation-induced oxidative stress via enhancing antioxidant effects in human HaCaT cells","volume":"24","author":"Fernando","year":"2016","journal-title":"Biomol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.bcp.2007.06.007","article-title":"Rosmarinic acid induces melanogenesis through protein kinase A activation signaling","volume":"74","author":"Lee","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.fct.2008.11.026","article-title":"Lozano, J.A. Rosmarinic acid, a photo-protective agent against UV and other ionizing radiations","volume":"47","author":"Gabaldon","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.det.2005.09.003","article-title":"Novel Emerging Sunscreen Technologies","volume":"24","author":"Tuchinda","year":"2006","journal-title":"Dermatol. Clin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.foodchem.2010.04.009","article-title":"Antioxidant properties of modified rutin esters by DPPH, reducing power, iron chelation and human low density lipoprotein assays","volume":"123","author":"Lue","year":"2010","journal-title":"Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Morocho-J\u00e1come, A.L., Santos, B.B., Carvalho, J.C.M., Almeida, T.S., Rijo, P., Velasco, M.V.R., Rosado, C., and Baby, A.R. (2022). Microalgae as a sustainable, natural-oriented and vegan dermocosmetic bioactive ingredient: The case of neochloris oleoabundans. Cosmetics, 9.","DOI":"10.3390\/cosmetics9010009"},{"key":"ref_16","unstructured":"Cosmetics Europe (2011). In Vitro Method for the Determination of the UVA Protection Factor and \u2018\u2018Critical Wavelength\u2019\u2019 Values of Sunscreen Products, COLIPA."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ruscinc, N., Morocho-J\u00e1come, A.L., Martinez, R.M., Magalh\u00e3es, W.V., Escudeiro, C.C., Giarolla, J., Rosado, C., Velasco, M.V.R., and Baby, A.R. (2022). Vaccinium myrtillus L. extract associated with octocrylene, bisoctrizole, and titanium dioxide: In vitro and in vivo tests to evaluate safety and efficacy. J. Cosmet. Dermatol, 1\u201310.","DOI":"10.1111\/jocd.14779"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1111\/jocd.13238","article-title":"Influence of Shea (Butyrospermum parkii) butter, TiO2 and ethylhexyl methoxycinnamate on physical parameters and in vitro photoprotective efficacy","volume":"19","author":"Sarruf","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1080\/03639040802277664","article-title":"Influence of urea, isopropanol, and propylene glycol on rutin in vitro release from cosmetic semisolid systems estimated by factorial design","volume":"35","author":"Baby","year":"2009","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1529-8019.2009.01289.x","article-title":"Photoprotection: A Review of the Current and Future Technologies","volume":"23","author":"Wang","year":"2010","journal-title":"Dermatol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3109\/07388551.2011.596804","article-title":"Rosmarinic acid and its derivatives: Biotechnology and applications Crit","volume":"32","author":"Bulgakov","year":"2012","journal-title":"Rev. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1016\/j.bbamem.2011.08.011","article-title":"The natural antioxidant rosmarinic acid spontaneously penetrates membranes to inhibit lipid peroxidation in situ","volume":"1808","author":"Fadel","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1055\/a-1301-8648","article-title":"Rosmarinic Acid-Human Pharmacokinetics and Health Benefits","volume":"87","author":"Hitl","year":"2021","journal-title":"Planta Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sutkowska, J., Hupert, N., Gawron, K., Strawa, J.W., Tomczyk, M., Forlino, A., and Galicka, A. (2021). The Stimulating Effect of Rosmarinic Acid and Extracts from Rosemary and Lemon Balm on Collagen Type I Biosynthesis in Osteogenesis Imperfecta Type I Skin Fibroblasts. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13070938"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9763","DOI":"10.3892\/mmr.2017.7804","article-title":"Protective effects of rosmarinic acid against hydrogen peroxide\u2014Induced cellular senescence and the inflammatory response in normal human dermal fibroblasts","volume":"16","author":"Hahn","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1016\/j.lfs.2006.06.042","article-title":"Phenolic compounds protect HepG2 cells from oxidative damage: Relevance of glutathione levels","volume":"79","author":"Lima","year":"2006","journal-title":"Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.jep.2010.01.062","article-title":"Identification of rosmarinic acid as the major active constituent in Cordia americana","volume":"128","author":"Geller","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.chroma.2020.461709","article-title":"Sequential extraction of carnosic acid, rosmarinic acid and pigments (carotenoids and chlorophylls) from Rosemary by online supercritical fluid extraction-supercritical fluid chromatography","volume":"1639","author":"Lefebvre","year":"2021","journal-title":"J. Chromatogr. A"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pattananandecha, T., Apichai, S., Julsrigival, J., Ungsurungsie, M., Kawasaki, N., and Saenjum, C. (2021). UVA-Irradiated Human Fibroblasts of Rosmarinic Acid. Plants, 10.","DOI":"10.3390\/plants10081648"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Matwiejczuk, N., Galicka, A., Zareba, I., and Brz\u00f3ska, M.M. (2020). The protective effect of rosmarinic acid against unfavorable influence of methylparaben and propylparaben on collagen in human skin fibroblasts. Nutrients, 12.","DOI":"10.3390\/nu12051282"},{"key":"ref_31","unstructured":"Fruet, A.C. (2015). Avalia\u00e7\u00e3o do Efeito Fotoprotetor de Compostos Fen\u00f3licos Sobre Culturas de C\u00e9lulas da pele Irradiadas por UVA e UVB. [Ph.D. Thesis, University of S\u00e3o Paulo]."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.36877\/pddbs.a0000027","article-title":"Model of experimentation for photoprotective properties of natural products against ultraviolet C (UVC) damage: A case study on rosmarinic acid","volume":"2","author":"Mahendra","year":"2019","journal-title":"Prog. Drug Discov. Biomed. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chen, Y., Zhang, X., Guo, Q., Liu, L., Li, C., Cao, L., Qin, Q., Zhao, M., and Wang, W. (2018). Effects of UV-B radiation on the content of bioactive components and the antioxidant activity of Prunella vulgaris L. Spica during development. Molecules., 23.","DOI":"10.3390\/molecules23050989"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Luna, A., Javier, \u00c1.-R., Oliveira, H., Motilva, V., and Talero, E. (2019). Fucoxanthin and rosmarinic acid combination has anti-inflammatory effects through regulation of NLRP3 inflammasome in UVB-exposed HaCaT keratinocytes. Mar. Drugs, 17.","DOI":"10.3390\/md17080451"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1559325820968413","article-title":"Rosmarinic acid prevents radiation-induced pulmonary fibrosis through attenuation of ROS\/MYPT1\/TGF\u03b21 signaling via miR-19b-3p","volume":"18","author":"Zhang","year":"2020","journal-title":"Dose-Response"},{"key":"ref_36","unstructured":"Bispo, M.O. (2022). Efic\u00e1cia Fotoprotetora do \u00c1cido Rosmar\u00ednico Associado a Filtros UVA e UVB. [Master\u2019s Thesis, University of S\u00e3o Paulo]."},{"key":"ref_37","unstructured":"Cosmetics Europe (2006). Methods for Testing Efficacy of Sunscreen Products, COLIPA."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/jocd.12123","article-title":"Natural products as photoprotection","volume":"14","author":"Saewan","year":"2015","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_39","first-page":"29","article-title":"Photoprotection of natural flavonoids","volume":"3","author":"Saewan","year":"2013","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1021\/np7007297","article-title":"Quercetin and rutin as potential sunscreen agents: Determination of efficacy by an in vitro method","volume":"71","author":"Choquenet","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.yrtph.2014.02.014","article-title":"Photoprotective characteristics of natural antioxidant polyphenols","volume":"69","author":"Stevanato","year":"2014","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1080\/03639045.2016.1236809","article-title":"Quality by design (QbD), Process Analytical Technology (PAT), and design of experiment applied to the development of multifunctional sunscreens","volume":"43","author":"Peres","year":"2017","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ijpharm.2018.10.015","article-title":"SPF enhancement provided by rutin in a multifunctional sunscreen","volume":"552","author":"Tomazelli","year":"2018","journal-title":"Int. J. Pharm."}],"container-title":["Cosmetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9284\/9\/2\/29\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:29:47Z","timestamp":1760135387000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9284\/9\/2\/29"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,28]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["cosmetics9020029"],"URL":"https:\/\/doi.org\/10.3390\/cosmetics9020029","relation":{},"ISSN":["2079-9284"],"issn-type":[{"value":"2079-9284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,28]]}}}