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However, quercetin exhibits a reduced aqueous solubility and stability, resulting in a low bioavailability that limits its therapeutic use. In this study, chitosan\/sulfonyl-ether-\u03b2-cyclodextrin (SBE-\u03b2-CD)-conjugated delivery systems have been explored in order to increase quercetin loading capacity, carriage, solubility and consequently bioavailability in cervical cancer cells. SBE-\u03b2-CD\/quercetin inclusion complexes were tested as well as chitosan\/SBE-\u03b2-CD\/quercetin-conjugated delivery systems, using two types of chitosan differing in molecular weight. Regarding characterization studies, HMW chitosan\/SBE-\u03b2-CD\/quercetin formulations have demonstrated the best results, which are obtaining nanoparticle sizes of 272.07 \u00b1 2.87 nm, a polydispersity index (PdI) of 0.287 \u00b1 0.011, a zeta potential of +38.0 \u00b1 1.34 mV and an encapsulation efficiency of approximately 99.9%. In vitro release studies were also performed for 5 kDa chitosan formulations, indicating a quercetin release of 9.6% and 57.53% at pH 7.4 and 5.8, respectively. IC50 values on HeLa cells indicated an increased cytotoxic effect with HMW chitosan\/SBE-\u03b2-CD\/quercetin delivery systems (43.55 \u03bcM), suggesting a remarkable improvement of quercetin bioavailability.<\/jats:p>","DOI":"10.3390\/pharmaceutics15030936","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T06:57:11Z","timestamp":1678777031000},"page":"936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Development and Characterization of Quercetin-Loaded Delivery Systems for Increasing Its Bioavailability in Cervical Cancer Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5595-204X","authenticated-orcid":false,"given":"Miguel","family":"Ferreira","sequence":"first","affiliation":[{"name":"CICS-UBI\u2014Health Science Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Diana","family":"Gomes","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Science Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA, 2819-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Departament of Chemistry, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9345-3193","authenticated-orcid":false,"given":"Miguel","family":"Neto","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Science Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6910-7576","authenticated-orcid":false,"given":"Lu\u00eds A.","family":"Passarinha","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Science Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA, 2819-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Departament of Chemistry, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"},{"name":"Laborat\u00f3rio de F\u00e1rmaco-Toxicologia-UBIMedical, Universidade da Beira Interior, 6200-284 Covilh\u00e3, Portugal"}]},{"given":"Diana","family":"Costa","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Science Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-7581","authenticated-orcid":false,"given":"\u00c2ngela","family":"Sousa","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Science Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dobrzynska, M., Napierala, M., and Florek, E. (2020). Flavonoid Nanoparticles: A Promising Approach for Cancer Therapy. 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