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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Dove Medical Press
2017
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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) |
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Lovastatin PLGA Direct pulp capping Medicine (General) R5-920 |
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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 |
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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 |
work_keys_str_mv |
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_version_ |
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