RRC ID 62048
著者 Terauchi M, Inada T, Tonegawa A, Tamura A, Yamaguchi S, Harada K, Yui N.
タイトル Supramolecular inclusion complexation of simvastatin with methylated β-cyclodextrins for promoting osteogenic differentiation.
ジャーナル Int J Biol Macromol
Abstract Statins are recognized as a potential candidate to induce the regeneration of bone. However, statins are a strongly hydrophobic drug and it is difficult to administer at the local sites. In this study, the inclusion complexes of simvastatin (SV) with hydroxypropyl-β-cyclodextrin (HP-β-CD) and randomly methylated β-cyclodextrin (RM-β-CD) were prepared to improve the water-solubility and the osteogenic differentiation ability of the inclusion complexes in MC3T3-E1 cells was investigated. The water-solubility of SV increased linearly upon the addition of both HP-β-CD and RM-β-CD, due to the formation of inclusion complexes. The osteogenic differentiation ability of the inclusion complexes were evaluated by the production of alkaline phosphatase (ALP) and late stage osteogenetic gene expression in MC3T3-E1 cells after 14 days of culture. As a result, the RM-β-CD/SV inclusion complexes showed significantly higher ALP production and the expression of bone sialoprotein (BSP) and osteocalcin (OCN) than the untreated and free SV-treated cells. Additionally, the production of bone morphogenetic protein-2 (BMP-2) from MC3T3-E1 cells after the treatment with RM-β-CD/SV inclusion complexes was significantly higher than the untreated and free SV-treated cells. Accordingly, it is concluded that the inclusion complexation of SV with RM-β-CD is a potential formulation for bone regenerative therapy to improve water-solubility and osteodifferentiation efficiency.
巻・号 93(Pt B)
ページ 1492-1498
公開日 2016-12-1
DOI 10.1016/j.ijbiomac.2016.01.114
PII S0141-8130(16)30113-1
PMID 26845478
MeSH Alkaline Phosphatase / metabolism Animals Cell Differentiation / drug effects* Cell Line Drug Evaluation, Preclinical Hydrophobic and Hydrophilic Interactions Mice Osteogenesis / drug effects Simvastatin / chemistry* Simvastatin / pharmacology Solubility beta-Cyclodextrins / chemistry* beta-Cyclodextrins / pharmacology
IF 5.162
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)