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Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth
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-glycol...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546772/ https://www.ncbi.nlm.nih.gov/pubmed/28814864 http://dx.doi.org/10.2147/IJN.S138410 |
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author | Lin, Hung-Pin Tu, Han-Ping Hsieh, Yu-Ping Lee, Bor-Shiunn |
author_facet | Lin, Hung-Pin Tu, Han-Ping Hsieh, Yu-Ping Lee, Bor-Shiunn |
author_sort | Lin, Hung-Pin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5546772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55467722017-08-16 Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth Lin, Hung-Pin Tu, Han-Ping Hsieh, Yu-Ping Lee, Bor-Shiunn Int J Nanomedicine Original Research 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. Dove Medical Press 2017-07-31 /pmc/articles/PMC5546772/ /pubmed/28814864 http://dx.doi.org/10.2147/IJN.S138410 Text en © 2017 Lin et al. 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 (http://creativecommons.org/licenses/by-nc/3.0/). 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. |
spellingShingle | Original Research Lin, Hung-Pin Tu, Han-Ping Hsieh, Yu-Ping Lee, Bor-Shiunn Controlled release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles for direct pulp capping in rat teeth |
title | 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_short | 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 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546772/ https://www.ncbi.nlm.nih.gov/pubmed/28814864 http://dx.doi.org/10.2147/IJN.S138410 |
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