应用含有顺铂和姜黄素的三层支架进行癌性骨再生。
Triple-layered scaffold containing cisplatin and curcumin applied for cancerous bone regeneration.
发表日期:2023 Aug 24
作者:
Nicha Thepsri, Jasadee Kaewsrichan
来源:
Bone & Joint Journal
摘要:
本研究制备了一种新型药物输送系统,并对其在癌性骨病治疗中的应用进行了评估。该系统由三个堆叠层构成,包括无药物层、载铂层和含姜黄素层。我们以前表征的生物材料——Zr-羟基磷灰石(Zr-HA)和碱处理的聚己内酯(改性PCL)作为药物载体的主要成分。通过包含改性PCL,调控载铂和Zr-HA之间的极性相互作用,从而增加了载铂的释放。使用β-环糊精(β-CD)包封姜黄素的方法改善姜黄素的溶解度和释放性能。根据扫描电镜照片,这种三维构建物具有内部互连孔隙的多孔结构。在浸泡于生理缓冲液和含胎牛血清的培养基中后,构建物上形成了大量磷灰石并吸附了蛋白质。采用最佳浓度的抗坏血酸和曲安奈德诱导骨髓基质细胞通过表达碱性磷酸酶等酶标志物转化为成骨细胞。制备的构建物具有成骨和诱导成骨能力。载铂和姜黄素的浓度在释放后24小时和3天分别达到了骨肉瘤SK-ES-1细胞和乳腺腺癌MCF-7细胞的IC50。这些癌细胞对联合应用载铂和姜黄素比每种药物单独应用更敏感。通过使用该药物载体替代缺失骨骼来重建新骨并消灭居住性癌细胞,我们提出了在缺失骨骼处发生骨再生的假设。将来需要通过动物模型来验证这个假设。
Novel drug delivery system was prepared and evaluated as for application in cancerous bone treatment. It had three stacked layers, including a drug-free layer, a cisplatin-loaded layer, and a curcumin-containing layer. Our previously characterized biomaterials, namely Zr-hydroxyapatite (Zr-HA) and alkaline-treated polycaprolactone (modified-PCL), were used as major components of the drug carrier. Polar-polar interactions between cisplatin and Zr-HA were modulated by the modified-PCL included, leading to increase of cisplatin release. Using β-cyclodextrin (β-CD) to entrap curcumin caused improvement of curcumin solubility and release. The 3D-construct was porous with internal interconnected pores according to SEM micrographs. Large amount of apatite was formed and proteins adsorbed on the scaffolds after immersed in physiologic buffer solution and in medium containing fetal bovine serum, respectively. Optimal concentrations of ascorbic acid and triamcinolone were used for induction of bone marrow stromal cells to become osteoblasts by expressing an enzyme marker, e.g., alkaline phosphatase. The prepared scaffolds were considered osteo-conductive and osteo-inductive. The concentrations of cisplatin and curcumin reached the IC50 of SK-ES-1 cells of osteosarcoma and MCF-7 cells of breast adenocarcinoma after 24 h and 3 days of release, respectively. These cancer cells were more sensitive to the combined cisplatin and curcumin than each of the drugs. Regeneration of new bone and execution of residential cancer cells in defected bone were proposed after replacing the lost bone by this established drug carrier. The assumption needs to be verified in the future using animal models.