Enhanced cellular uptake and osteogenic differentiation efficiency of melatonin by inclusion complexation with 2-hydroxypropyl β-cyclodextrin
Enhanced cellular uptake and osteogenic differentiation efficiency of melatonin by inclusion complexation with 2-hydroxypropyl β-cyclodextrin
复制标题
通过与 2-羟丙基 β-环糊精包合络合增强褪黑激素的细胞摄取和成骨分化效率
DOI：
10.1016/j.ijpharm.2018.05.063
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发表时间：
2018
影响因子：
5.8
通讯作者：
Yui Nobuhiko
中科院分区：
文献类型：
--
作者：
Terauchi Masahiko;Tamura Atsushi;Yamaguchi Satoshi;Yui Nobuhiko
褪黑激素（MLT）是一种由松果体分泌的激素，被认为是刺激骨再生的潜在候选者。然而，由于其疏水性，施用MLT以刺激骨再生是困难的。为了提高MLT的水溶性，制备了MLT与2-羟丙基β-环糊精（HP-β-CD）的包合物，并研究了该包合物对MC 3 T3-E1细胞成骨分化的影响。通过核磁共振氢谱、碳谱和广角X射线衍射证实了包合物的形成。加入HP-β-CD后，MLT的水溶解度线性增加，这是因为形成了包合物。此外，HP-β-CD/MLT包合物处理的细胞对MLT的摄取量高于游离MLT处理的细胞。此外，HP-β-CD/MLT包合物处理MC 3 T3-E1细胞后，碱性磷酸酶活性和矿化基质沉积均较MLT处理组和未处理组增加。此外，HP-β-CD/MLT包合物处理的细胞成骨分化基因的表达水平高于未处理和游离MLT处理的细胞。因此，这些结果表明，MLT与HP-β-CD的包合物由于其改善的溶解性和增强的成骨分化效率而将是一种潜在的骨再生制剂。
Melatonin (MLT), a hormone secreted from the pineal gland, is recognized as a potential candidate for stimulation of bone regeneration. However, because of its hydrophobicity, the administration of MLT to stimulate bone regeneration is difficult. In this study, an inclusion complex of MLT with 2-hydroxypropyl β-cyclodextrin (HP-β-CD) was prepared to improve the water solubility, and the osteogenic differentiation ability of the inclusion complex was investigated in MC3T3-E1 cells. The formation of HP-β-CD/MLT inclusion complex was confirmed by1H and13C nuclear magnetic resonance spectroscopy and wide-angle X-ray diffraction. The water solubility of MLT increased linearly upon addition of HP-β-CD because of the formation of the inclusion complex. Additionally, treatment of the cells with HP-β-CD/MLT inclusion complex showed higher uptake amount of MLT than that treated with free MLT. In addition, treatment of MC3T3-E1 cells with HP-β-CD/MLT inclusion complex increased alkaline phosphatase activity and mineralized matrix deposition, compared to that in free MLT-treated and untreated cells. Furthermore, cells treated with HP-β-CD/MLT inclusion complex exhibited higher expression levels of osteogenic differentiation genes than those in the untreated and free MLT-treated cells. Accordingly, these results suggested that inclusion complexation of MLT with HP-β-CD would be a potential formulation for bone regeneration because of its improved solubility and enhanced osteogenic differentiation efficiency.