Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair

Authors Tai IC, Fu YC, Wang CK, Chang JK, Ho ML

Received 19 May 2013

Accepted for publication 10 July 2013

Published 11 October 2013 Volume 2013:8(1) Pages 3895—3905

DOI https://doi.org/10.2147/IJN.S48694

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

I-Chun Tai,1–3 Yin-Chih Fu,3,4 Chih-Kuang Wang,3,5 Je-Ken Chang,3,4,6 Mei-Ling Ho1–3

1Graduate Institute of Medicine, 2Department of Physiology, 3Orthopedic Research Center, College of Medicine, 4Department of Orthopedics, 5Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, 6Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan

Abstract: Statins are used clinically for reduction of cholesterol synthesis to prevent cardiovascular disease. Previous in vitro and in vivo studies have shown that statins stimulate bone formation. However, orally administered statins may be degraded during first-pass metabolism in the liver. This study aimed to prevent this degradation by developing a locally administered formulation of simvastatin that is encapsulated in poly(lactic-co-glycolic acid)/hydroxyapatite (SIM/PLGA/HAp) microspheres with controlled-release properties. The effect of this formulation of simvastatin on bone repair was tested using a mouse model of gap fracture bridging with a graft of necrotic bone. The simvastatin released over 12 days from 3 mg and 5 mg of SIM/PLGA/HAp was 0.03–1.6 µg/day and 0.05–2.6 µg/day, respectively. SIM/PLGA/HAp significantly stimulated callus formation around the repaired area and increased neovascularization and cell ingrowth in the grafted necrotic bone at week 2 after surgery. At week 4, both 3 mg and 5 mg of SIM/PLGA/HAp increased neovascularization, but only 5 mg SIM/PLGA/HAp enhanced cell ingrowth into the necrotic bone. The low dose of simvastatin released from SIM/PLGA/HAp enhanced initial callus formation, neovascularization, and cell ingrowth in the grafted bone, indicating that SIM/PLGA/HAp facilitates bone regeneration. We suggest that SIM/PLGA/HAp should be developed as an osteoinductive agent to treat osteonecrosis or in combination with an osteoconductive scaffold to treat severe bone defects.

Keywords: statin, controlled release, poly(lactic-co-glycolic acid), microspheres, bone fracture

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other articles by this author:

Simvastatin enhances Rho/actin/cell rigidity pathway contributing to mesenchymal stem cells’ osteogenic differentiation

Tai IC, Wang YH, Chen CH, Chuang SC, Chang JK, Ho ML

International Journal of Nanomedicine 2015, 10:5881-5894

Published Date: 21 September 2015

Readers of this article also read:

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Topical diclofenac in the treatment of osteoarthritis of the knee

Niklas Schuelert, Fiona A Russell, Jason J McDougall

Orthopedic Research and Reviews 2011, 3:1-8

Published Date: 6 February 2011