title: Supramolecular inclusion complexation of simvastatin with methylated β-cyclodextrins for promoting osteogenic differentiation.
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.
authors: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan; Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
authors: Masahiko
authors: M
authors: Terauchi
authors: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan; Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
authors: Takasuke
authors: T
authors: Inada
authors: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
authors: Asato
authors: A
authors: Tonegawa
authors: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan. Electronic address: tamura.org@tmd.ac.jp.
authors: Atsushi
authors: A
authors: Tamura
authors: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan.
authors: Satoshi
authors: S
authors: Yamaguchi
authors: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan.
authors: Kiyoshi
authors: K
authors: Harada
authors: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
authors: Nobuhiko
authors: N
authors: Yui
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D019821:Simvastatin / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D047392:beta-Cyclodextrins; D019821:Simvastatin; D000469:Alkaline Phosphatase
keywords: Bone regeneration; Inclusion complex; Osteogenetic differentiation; Simvastatin; β-cyclodextrin