Supramolecular inclusion complexation of simvastatin with methylated β-cyclodextrins for promoting osteogenic differentiation

• Published in: International journal of biological macromolecules Vol. 93; no. Pt B; pp. 1492 - 1498
• Main Authors: Terauchi, Masahiko, Inada, Takasuke, Tonegawa, Asato, Tamura, Atsushi, Yamaguchi, Satoshi, Harada, Kiyoshi, Yui, Nobuhiko
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2016
• Subjects: Alkaline Phosphatase - metabolism; Animals; beta-Cyclodextrins - chemistry; beta-Cyclodextrins - pharmacology; Bone regeneration; Cell Differentiation - drug effects; Cell Line; Drug Evaluation, Preclinical; Hydrophobic and Hydrophilic Interactions; Inclusion complex; Mice; Osteogenesis - drug effects; Osteogenetic differentiation; Simvastatin; Simvastatin - chemistry; Simvastatin - pharmacology; Solubility; β-cyclodextrin; Osteogenetic differentiation; Bone regeneration; β-cyclodextrin; Simvastatin; Inclusion complex
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2016.01.114

[Display omitted] 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.