Ferreira Miguel, Gomes Diana, Neto Miguel, Passarinha Luís A, Costa Diana, Sousa Ângela
CICS-UBI-Health Science Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
Associate Laboratory i4HB-Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA, 2819-516 Caparica, Portugal.
Pharmaceutics. 2023 Mar 14;15(3):936. doi: 10.3390/pharmaceutics15030936.
Quercetin is a natural flavonoid with high anticancer activity, especially for related-HPV cancers such as cervical cancer. 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-β-cyclodextrin (SBE-β-CD)-conjugated delivery systems have been explored in order to increase quercetin loading capacity, carriage, solubility and consequently bioavailability in cervical cancer cells. SBE-β-CD/quercetin inclusion complexes were tested as well as chitosan/SBE-β-CD/quercetin-conjugated delivery systems, using two types of chitosan differing in molecular weight. Regarding characterization studies, HMW chitosan/SBE-β-CD/quercetin formulations have demonstrated the best results, which are obtaining nanoparticle sizes of 272.07 ± 2.87 nm, a polydispersity index (PdI) of 0.287 ± 0.011, a zeta potential of +38.0 ± 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. IC values on HeLa cells indicated an increased cytotoxic effect with HMW chitosan/SBE-β-CD/quercetin delivery systems (43.55 μM), suggesting a remarkable improvement of quercetin bioavailability.
槲皮素是一种具有高抗癌活性的天然黄酮类化合物，尤其对与HPV相关的癌症如宫颈癌有效。然而，槲皮素的水溶性和稳定性较低，导致其生物利用度低，限制了其治疗用途。在本研究中，探索了壳聚糖/磺酰醚-β-环糊精（SBE-β-CD）共轭递送系统，以提高槲皮素在宫颈癌细胞中的负载能力、携带能力、溶解度以及生物利用度。测试了SBE-β-CD/槲皮素包合物以及壳聚糖/SBE-β-CD/槲皮素共轭递送系统，使用了两种分子量不同的壳聚糖。关于表征研究，高分子量壳聚糖/SBE-β-CD/槲皮素制剂显示出最佳结果，纳米颗粒尺寸为272.07±2.87nm，多分散指数（PdI）为0.287±0.011，ζ电位为+38.0±1.34mV，包封率约为99.9%。还对5kDa壳聚糖制剂进行了体外释放研究，结果表明在pH 7.4和5.8时槲皮素的释放率分别为9.6%和57.53%。对HeLa细胞的IC值表明，高分子量壳聚糖/SBE-β-CD/槲皮素递送系统（43.55μM）的细胞毒性作用增强，表明槲皮素的生物利用度有显著提高。
