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Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity
PURPOSE: The aim of this study was to develop a means of improving the bioavailability and anticancer activity of urushiol by developing an urushiol-loaded novel tumor-targeted micelle delivery system based on amphiphilic block copolymer poly(ethylene glycol)-b-poly-(β-amino ester) (mPEG-PBAE). MATE...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359855/ https://www.ncbi.nlm.nih.gov/pubmed/32764919 http://dx.doi.org/10.2147/IJN.S250564 |
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author | Zhou, Hao Qi, Zhiwen Xue, Xingying Wang, Chengzhang |
author_facet | Zhou, Hao Qi, Zhiwen Xue, Xingying Wang, Chengzhang |
author_sort | Zhou, Hao |
collection | PubMed |
description | PURPOSE: The aim of this study was to develop a means of improving the bioavailability and anticancer activity of urushiol by developing an urushiol-loaded novel tumor-targeted micelle delivery system based on amphiphilic block copolymer poly(ethylene glycol)-b-poly-(β-amino ester) (mPEG-PBAE). MATERIALS AND METHODS: We synthesized four different mPEG-PBAE copolymers using mPEG-NH(2) with different molecular weights or hydrophobicity levels. Of these, we selected the mPEG(5000)-PBAE-C(12) polymer and used it to develop an optimized means of preparing urushiol-loaded micelles. Response surface methodology was used to optimize this formulation process. The micellar properties, including particle size, pH sensitivity, drug release dynamics, and critical micelle concentrations, were characterized. We further used the MCF-7 human breast cancer cell line to explore the cytotoxicity of these micelles in vitro and assessed their pharmacokinetics, tissue distribution, and antitumor activity in vivo. RESULTS: The resulting micelles had a mean particle size of 160.1 nm, a DL value of 23.45%, and an EE value of 80.68%. These micelles were found to release their contents in a pH-sensitive manner in vitro, with drug release being significantly accelerated at pH 5.0 (98.74% in 72 h) without any associated burst release. We found that urushiol-loaded micelles were significantly better at inducing MCF-7 cell cytotoxicity compared with free urushiol, with an IC(50) of 1.21 mg/L. When these micelles were administered to tumor model animals in vivo, pharmacokinetic analysis revealed that the total AUC and MRT of these micelles were 2.28- and 2.53-fold higher than that of free urushiol, respectively. Tissue distribution analyses further revealed these micelles to mediate significantly enhanced tumor urushiol accumulation. CONCLUSION: The pH-responsive urushiol-loaded micelles described in this study may be ideally suited for clinical use for the treatment of breast cancer. |
format | Online Article Text |
id | pubmed-7359855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-73598552020-08-05 Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity Zhou, Hao Qi, Zhiwen Xue, Xingying Wang, Chengzhang Int J Nanomedicine Original Research PURPOSE: The aim of this study was to develop a means of improving the bioavailability and anticancer activity of urushiol by developing an urushiol-loaded novel tumor-targeted micelle delivery system based on amphiphilic block copolymer poly(ethylene glycol)-b-poly-(β-amino ester) (mPEG-PBAE). MATERIALS AND METHODS: We synthesized four different mPEG-PBAE copolymers using mPEG-NH(2) with different molecular weights or hydrophobicity levels. Of these, we selected the mPEG(5000)-PBAE-C(12) polymer and used it to develop an optimized means of preparing urushiol-loaded micelles. Response surface methodology was used to optimize this formulation process. The micellar properties, including particle size, pH sensitivity, drug release dynamics, and critical micelle concentrations, were characterized. We further used the MCF-7 human breast cancer cell line to explore the cytotoxicity of these micelles in vitro and assessed their pharmacokinetics, tissue distribution, and antitumor activity in vivo. RESULTS: The resulting micelles had a mean particle size of 160.1 nm, a DL value of 23.45%, and an EE value of 80.68%. These micelles were found to release their contents in a pH-sensitive manner in vitro, with drug release being significantly accelerated at pH 5.0 (98.74% in 72 h) without any associated burst release. We found that urushiol-loaded micelles were significantly better at inducing MCF-7 cell cytotoxicity compared with free urushiol, with an IC(50) of 1.21 mg/L. When these micelles were administered to tumor model animals in vivo, pharmacokinetic analysis revealed that the total AUC and MRT of these micelles were 2.28- and 2.53-fold higher than that of free urushiol, respectively. Tissue distribution analyses further revealed these micelles to mediate significantly enhanced tumor urushiol accumulation. CONCLUSION: The pH-responsive urushiol-loaded micelles described in this study may be ideally suited for clinical use for the treatment of breast cancer. Dove 2020-05-29 /pmc/articles/PMC7359855/ /pubmed/32764919 http://dx.doi.org/10.2147/IJN.S250564 Text en © 2020 Zhou et al. http://creativecommons.org/licenses/by-nc/3.0/ 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Zhou, Hao Qi, Zhiwen Xue, Xingying Wang, Chengzhang Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity |
title | Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity |
title_full | Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity |
title_fullStr | Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity |
title_full_unstemmed | Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity |
title_short | Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity |
title_sort | novel ph-sensitive urushiol-loaded polymeric micelles for enhanced anticancer activity |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359855/ https://www.ncbi.nlm.nih.gov/pubmed/32764919 http://dx.doi.org/10.2147/IJN.S250564 |
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