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

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 o...

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Autores principales:	Tai IC, Fu YC, Wang CK, Chang JK, Ho ML
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bfe1ce865f134eb08a4bb4a4efc04faf
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spelling	oai:doaj.org-article:bfe1ce865f134eb08a4bb4a4efc04faf2021-12-02T04:59:15ZLocal delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair1176-91141178-2013https://doaj.org/article/bfe1ce865f134eb08a4bb4a4efc04faf2013-10-01T00:00:00Zhttp://www.dovepress.com/local-delivery-of-controlled-release-simvastatinplgahap-microspheres-e-a14678https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013I-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 fractureTai ICFu YCWang CKChang JKHo MLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss Issue 1, Pp 3895-3905 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Tai IC Fu YC Wang CK Chang JK Ho ML Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair
description	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
format	article
author	Tai IC Fu YC Wang CK Chang JK Ho ML
author_facet	Tai IC Fu YC Wang CK Chang JK Ho ML
author_sort	Tai IC
title	Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair
title_short	Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair
title_full	Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair
title_fullStr	Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair
title_full_unstemmed	Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair
title_sort	local delivery of controlled-release simvastatin/plga/hap microspheres enhances bone repair
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/bfe1ce865f134eb08a4bb4a4efc04faf
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Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair

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