Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth

Hung-Pin Lin,1,2,* Han-Ping Tu,3,* Yu-Ping Hsieh,4 Bor-Shiunn Lee3 1Department of Dentistry, MacKay Memorial Hospital, 2Department of Dentistry, School of Dentistry, National Taiwan University, 3Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University and National Taiwan...

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Autores principales: Lin HP, Tu HP, Hsieh YP, Lee BS
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:8a7a0d6dc8c244ab8d5cbc613bda7f492021-12-02T01:49:53ZControlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth1178-2013https://doaj.org/article/8a7a0d6dc8c244ab8d5cbc613bda7f492017-07-01T00:00:00Zhttps://www.dovepress.com/controlled-release--of-lovastatin-from-polylactic-co-glycolic-acid-nan-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hung-Pin Lin,1,2,* Han-Ping Tu,3,* Yu-Ping Hsieh,4 Bor-Shiunn Lee3 1Department of Dentistry, MacKay Memorial Hospital, 2Department of Dentistry, School of Dentistry, National Taiwan University, 3Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University and National Taiwan University Hospital, 4School of Dentistry, National Taiwan University, Taipei, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Statin at appropriate concentrations has been shown to induce odontoblastic differentiation, dentinogenesis, and angiogenesis. However, using a carrier to control statin release might reduce toxicity and enhance its therapeutic effects. The aim of this study was to prepare poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles that contain lovastatin for application in direct pulp capping. The PLGA–lovastatin particle size was determined using dynamic light scattering measurements and transmission electron microscopy. In addition, the release of lovastatin was quantified using a UV–Vis spectrophotometer. The cytotoxicity and alkaline phosphatase (ALP) activity of PLGA–lovastatin nanoparticles on human dental pulp cells were investigated. Moreover, a real-time polymerase chain reaction (PCR) assay, Western blot analysis, and an enzyme-linked immunosorbent assay (ELISA) were used to examine the osteogenesis gene and protein expression of dentin sialophosphoprotein (DSPP), dentin matrix acidic phosphoprotein 1 (DMP1), and osteocalcin (OCN). Finally, PLGA–lovastatin nanoparticles and mineral trioxide aggregate (MTA) were compared as direct pulp capping materials in Wistar rat teeth. The results showed that the median diameter of PLGA–lovastatin nanoparticles was 174.8 nm and the cumulative lovastatin release was 92% at the 44th day. PLGA–lovastatin nanoparticles demonstrated considerably a lower cytotoxicity than free lovastatin at 5, 9, and 13 days of culture. For ALP activity, the ALP amount of PLGA–lovastatin (100 µg/mL) was significantly higher than that of the other groups for 9 and 13 days of culture. The real-time PCR assay, Western blot analysis, and ELISA assay showed that PLGA–lovastatin (100 µg/mL) induced the highest mRNA and protein expression of DSPP, DMP1, and OCN in pulp cells. Histological evaluation of the animal studies revealed that MTA was superior to the PLGA–lovastatin in stimulating the formation of tubular dentin in an observation period of 2 weeks. However, in an observation period of 4 weeks, it was evident that the PLGA–lovastatin and MTA were competitive in the formation of tubular reparative dentin and a complete dentinal bridge. Keywords: lovastatin, PLGA, direct pulp cappingLin HPTu HPHsieh YPLee BSDove Medical PressarticleLovastatinPLGADirect pulp cappingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5473-5485 (2017)
institution DOAJ
collection DOAJ
language EN
topic Lovastatin
PLGA
Direct pulp capping
Medicine (General)
R5-920
spellingShingle Lovastatin
PLGA
Direct pulp capping
Medicine (General)
R5-920
Lin HP
Tu HP
Hsieh YP
Lee BS
Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth
description Hung-Pin Lin,1,2,* Han-Ping Tu,3,* Yu-Ping Hsieh,4 Bor-Shiunn Lee3 1Department of Dentistry, MacKay Memorial Hospital, 2Department of Dentistry, School of Dentistry, National Taiwan University, 3Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University and National Taiwan University Hospital, 4School of Dentistry, National Taiwan University, Taipei, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Statin at appropriate concentrations has been shown to induce odontoblastic differentiation, dentinogenesis, and angiogenesis. However, using a carrier to control statin release might reduce toxicity and enhance its therapeutic effects. The aim of this study was to prepare poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles that contain lovastatin for application in direct pulp capping. The PLGA–lovastatin particle size was determined using dynamic light scattering measurements and transmission electron microscopy. In addition, the release of lovastatin was quantified using a UV–Vis spectrophotometer. The cytotoxicity and alkaline phosphatase (ALP) activity of PLGA–lovastatin nanoparticles on human dental pulp cells were investigated. Moreover, a real-time polymerase chain reaction (PCR) assay, Western blot analysis, and an enzyme-linked immunosorbent assay (ELISA) were used to examine the osteogenesis gene and protein expression of dentin sialophosphoprotein (DSPP), dentin matrix acidic phosphoprotein 1 (DMP1), and osteocalcin (OCN). Finally, PLGA–lovastatin nanoparticles and mineral trioxide aggregate (MTA) were compared as direct pulp capping materials in Wistar rat teeth. The results showed that the median diameter of PLGA–lovastatin nanoparticles was 174.8 nm and the cumulative lovastatin release was 92% at the 44th day. PLGA–lovastatin nanoparticles demonstrated considerably a lower cytotoxicity than free lovastatin at 5, 9, and 13 days of culture. For ALP activity, the ALP amount of PLGA–lovastatin (100 µg/mL) was significantly higher than that of the other groups for 9 and 13 days of culture. The real-time PCR assay, Western blot analysis, and ELISA assay showed that PLGA–lovastatin (100 µg/mL) induced the highest mRNA and protein expression of DSPP, DMP1, and OCN in pulp cells. Histological evaluation of the animal studies revealed that MTA was superior to the PLGA–lovastatin in stimulating the formation of tubular dentin in an observation period of 2 weeks. However, in an observation period of 4 weeks, it was evident that the PLGA–lovastatin and MTA were competitive in the formation of tubular reparative dentin and a complete dentinal bridge. Keywords: lovastatin, PLGA, direct pulp capping
format article
author Lin HP
Tu HP
Hsieh YP
Lee BS
author_facet Lin HP
Tu HP
Hsieh YP
Lee BS
author_sort Lin HP
title Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth
title_short Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth
title_full Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth
title_fullStr Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth
title_full_unstemmed Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth
title_sort controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/8a7a0d6dc8c244ab8d5cbc613bda7f49
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AT hsiehyp controlledreleaseoflovastatinfrompolylacticcoglycolicacidnanoparticlesfordirectpulpcappinginratteeth
AT leebs controlledreleaseoflovastatinfrompolylacticcoglycolicacidnanoparticlesfordirectpulpcappinginratteeth
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