In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration

Abstract

Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications.

Simvastatin exerts antiproliferative and differentiating effects on MG63 osteoblast‐like cells: Morphological and immunocytochemical study

“…Statin consumption was recently associated with lower tooth loss over time in a prospective epidemiologic study with 5 year follow‐up in a European population . Research is ongoing into the optimal statin concentrations to achieve anti‐inflammatory and bone anabolic effects in the local treatment of periodontal lesions; various carriers and drug delivery systems have been used, including the application of statins as bioactive agents on implant surfaces …”

“…34 Research is ongoing into the optimal statin concentrations to achieve anti-inflammatory and bone anabolic effects in the local treatment of periodontal lesions; various carriers and drug delivery systems have been used, including the application of statins as bioactive agents on implant surfaces. [35][36][37] The proliferation and cell functions exhibited by osteosarcoma cells may not be fully representative of those in human primary osteoblasts, given reported differences between them. 38 Nevertheless, the MG63 cell line has been widely used as an in vitro model for bone research, and findings on the proliferation of these cells have proven comparable to observations in primary human osteoblasts.…”

Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity

“…Simvastatin, known as a 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) reductase inhibitor, is widely used to decrease serum cholesterol because of its safe and effective treatment (Bjornsson, ; Stellaard & Lutjohann, ). Apart from cholesterol‐lowering effects, simvastatin is also found to promote osteogenic differentiation of BMSCs and suppress osteoclastic differentiation in bone tissue (Tai et al, ; Xu et al, ; Yue et al, ). Simvastatin accelerates bone regeneration in bone defects in ovariectomized rats by local application or oral administration (Bing et al, ; Niu, Ding, & Zhang, ) and promotes osseointegration around implants in animal studies (Sendyk, Deboni, Pannuti, Naclerio‐Homem, & Wennerberg, ).…”

The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells

“…11 We also confirmed by in vivo experiments that the nanoformulations of SV showed a stronger effect on the formation of new bone in a rabbit skull defect area than SV. 12 To date, the potential mechanisms by which SVNs significantly enhance the efficacy of SV in promoting osteogenesis have not been reported.…”