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Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.

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Title: Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.
Authors: Lin, Ts-Ting1, Gao, Dong-Yu1, Liu, Ya-Chi1, Sung, Yun-Chieh1, Wan, Dehui1, Liu, Jia-Yu1, Chiang, Tsaiyu1, Wang, Liying1, Chen, Yunching1 yunching@mx.nthu.edu.tw
Source: Journal of Controlled Release. Jan2016, Vol. 221, p62-70. 9p.
Subjects: Treatment of cirrhosis of the liver, Sorafenib, Nanomedicine, Treatment effectiveness, Laboratory mice
Abstract: Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co-glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl 4 -induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs) — PEG-PLGA NPs (PEG-PLGA/PLGA = 10/0) and PEG-PLGA/PLGA NPs (PEG-PLGA/PLGA = 5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4 weeks efficiently ameliorated liver fibrosis, as indicated by decreased α-smooth muscle actin (α-SMA) content and collagen production in the livers of CCl 4 -treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
An: 111928519
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PubType: Academic Journal
PubTypeId: academicJournal
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  Data: Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.
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  Data: <searchLink fieldCode="AR" term="%22Lin%2C+Ts-Ting%22">Lin, Ts-Ting</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Gao%2C+Dong-Yu%22">Gao, Dong-Yu</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Liu%2C+Ya-Chi%22">Liu, Ya-Chi</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Sung%2C+Yun-Chieh%22">Sung, Yun-Chieh</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Wan%2C+Dehui%22">Wan, Dehui</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Liu%2C+Jia-Yu%22">Liu, Jia-Yu</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chiang%2C+Tsaiyu%22">Chiang, Tsaiyu</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Wang%2C+Liying%22">Wang, Liying</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chen%2C+Yunching%22">Chen, Yunching</searchLink><relatesTo>1</relatesTo><i> yunching@mx.nthu.edu.tw</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Controlled+Release%22">Journal of Controlled Release</searchLink>. Jan2016, Vol. 221, p62-70. 9p.
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  Data: <searchLink fieldCode="DE" term="%22Treatment+of+cirrhosis+of+the+liver%22">Treatment of cirrhosis of the liver</searchLink><br /><searchLink fieldCode="DE" term="%22Sorafenib%22">Sorafenib</searchLink><br /><searchLink fieldCode="DE" term="%22Nanomedicine%22">Nanomedicine</searchLink><br /><searchLink fieldCode="DE" term="%22Treatment+effectiveness%22">Treatment effectiveness</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+mice%22">Laboratory mice</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co-glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl 4 -induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs) — PEG-PLGA NPs (PEG-PLGA/PLGA = 10/0) and PEG-PLGA/PLGA NPs (PEG-PLGA/PLGA = 5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4 weeks efficiently ameliorated liver fibrosis, as indicated by decreased α-smooth muscle actin (α-SMA) content and collagen production in the livers of CCl 4 -treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1016/j.jconrel.2015.11.003
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        Text: English
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        PageCount: 9
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      – SubjectFull: Treatment of cirrhosis of the liver
        Type: general
      – SubjectFull: Sorafenib
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      – SubjectFull: Nanomedicine
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      – SubjectFull: Treatment effectiveness
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      – SubjectFull: Laboratory mice
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      – TitleFull: Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.
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              M: 01
              Text: Jan2016
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