Department of Chemistry "G. Ciamician", University of Bologna, via Selmi 2, Bologna 40126, Italy.
Laboratory of Preclinical and Surgical Studies, Research Institute Codivilla Putti - Rizzoli Orthopaedic Institute, via di Barbiano 1/10, Bologna 40136, Italy.
J Biomed Mater Res A. 2017 Dec;105(12):3293-3303. doi: 10.1002/jbm.a.36192. Epub 2017 Sep 15.
In spite of its remarkable anti-oxidant, anti-inflammatory, anti-cancer properties and its possible inhibition activity towards bone resorption, quercetin therapeutic use is limited by its poor bioavailability. Herein we developed a new multifunctionalized system for the local administration of quercetin and alendronate, one of the most potent anti-osteoporotic drugs, with the aim to get a material with enhanced properties. To this purpose we loaded quercetin on hydroxyapatite functionalized with alendronate, as well as on hydroxyapatite. Characterization was performed by means of X-ray diffraction, FT-IR and Raman spectroscopies, thermogravimetric and spectrophotometric analyses. Loading of quercetin from hydro-alcoholic solution increased with time and reached a constant value of about 5 weight% on both substrates, without causing significant structural and morphological modifications. Quercetin functionalized materials exhibit relevant anti-oxidant properties, in agreement with their high radical scavenging activity, and a quercetin sustained release in phosphate buffer. In vitro osteoblast and osteoclast co-culture in a microenvironment altered by oxidative stress shows that both alendronate and quercetin significantly reduce osteoclast viability, whereas they are able to counteract the negative effect of oxidative stress on osteoblast viability and differentiation, suggesting that their relative amount in the functionalized materials can be utilized to tailor bone cells response. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3293-3303, 2017.
尽管槲皮素具有显著的抗氧化、抗炎、抗癌特性，并且可能抑制骨吸收，但由于其生物利用度低，其治疗用途受到限制。在此，我们开发了一种新的多功能系统，用于局部给予槲皮素和阿仑膦酸钠（一种最有效的抗骨质疏松药物之一），目的是获得具有增强性能的材料。为此，我们将槲皮素负载到用阿仑膦酸钠功能化的羟基磷灰石上，以及负载到羟基磷灰石上。通过 X 射线衍射、傅里叶变换红外和拉曼光谱、热重分析和分光光度分析对其进行了表征。在水醇溶液中，随着时间的延长，负载在两种基质上的槲皮素的含量均增加，并达到约 5wt%的恒定值，而不会引起明显的结构和形态变化。功能化材料具有显著的抗氧化性能，与其高自由基清除活性一致，并在磷酸盐缓冲液中具有持续释放的槲皮素。在体外氧化应激改变的成骨细胞和成骨细胞共培养实验中，阿仑膦酸钠和槲皮素均能显著降低破骨细胞的活力，而它们能够抵消氧化应激对成骨细胞活力和分化的负面影响，这表明功能化材料中它们的相对含量可用于调节骨细胞的反应。 © 2017 威利父子公司。J 生物医学材料研究部分 A：105A：3293-3303，2017。
