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Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy therapy
INTRODUCTION: Diabetic nephropathy (DN) is the primary root of morbidity and mortality in diabetic patients. Unfortunately, currently, no effective therapeutic strategies are available to ameliorate and reverse the progression of DN. Rhein (RH) is an anthraquinone derivative extracted from herbal me...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016261/ https://www.ncbi.nlm.nih.gov/pubmed/29950832 http://dx.doi.org/10.2147/IJN.S166445 |
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author | Chen, Danfei Han, Shunping Zhu, Yongqin Hu, Fang Wei, Yinghui Wang, Guowei |
author_facet | Chen, Danfei Han, Shunping Zhu, Yongqin Hu, Fang Wei, Yinghui Wang, Guowei |
author_sort | Chen, Danfei |
collection | PubMed |
description | INTRODUCTION: Diabetic nephropathy (DN) is the primary root of morbidity and mortality in diabetic patients. Unfortunately, currently, no effective therapeutic strategies are available to ameliorate and reverse the progression of DN. Rhein (RH) is an anthraquinone derivative extracted from herbal medicines with various pharmacological effects on DN. However, its clinical administration is limited by its poor solubility, low bioavailability, reduced distribution into the kidney and adverse effects. METHODS AND RESULTS: To improve the delivery of RH into kidney and the therapeutic effect on DN, we synthesized and utilized polyethyleneglycol-co-polycaprolactone-co-polyethylenimine triblock amphiphilic polymers to prepare RH-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles (PPP-RH-NPs). PPP-RH-NP size was optimized to 75 ± 25 nm for kidney-targeted drug delivery; the positive zeta potential allowed an effective cellular uptake and the polyethylenimine amine groups facilitate the endosomal escape quickly. The distribution and pharmacodynamics of PPP-RH-NPs were studied in a streptozocin-induced DN model, which explicitly demonstrated kidney-targeted distribution and improved the therapeutic effects of RH on DN by ameliorating several pathological indicators. CONCLUSION: Therefore, this study not only stimulates further clinical research on RH but also, more importantly, proposes a promising DN therapy consisting of an effective kidney-targeted drug delivery. |
format | Online Article Text |
id | pubmed-6016261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60162612018-06-27 Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy therapy Chen, Danfei Han, Shunping Zhu, Yongqin Hu, Fang Wei, Yinghui Wang, Guowei Int J Nanomedicine Original Research INTRODUCTION: Diabetic nephropathy (DN) is the primary root of morbidity and mortality in diabetic patients. Unfortunately, currently, no effective therapeutic strategies are available to ameliorate and reverse the progression of DN. Rhein (RH) is an anthraquinone derivative extracted from herbal medicines with various pharmacological effects on DN. However, its clinical administration is limited by its poor solubility, low bioavailability, reduced distribution into the kidney and adverse effects. METHODS AND RESULTS: To improve the delivery of RH into kidney and the therapeutic effect on DN, we synthesized and utilized polyethyleneglycol-co-polycaprolactone-co-polyethylenimine triblock amphiphilic polymers to prepare RH-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles (PPP-RH-NPs). PPP-RH-NP size was optimized to 75 ± 25 nm for kidney-targeted drug delivery; the positive zeta potential allowed an effective cellular uptake and the polyethylenimine amine groups facilitate the endosomal escape quickly. The distribution and pharmacodynamics of PPP-RH-NPs were studied in a streptozocin-induced DN model, which explicitly demonstrated kidney-targeted distribution and improved the therapeutic effects of RH on DN by ameliorating several pathological indicators. CONCLUSION: Therefore, this study not only stimulates further clinical research on RH but also, more importantly, proposes a promising DN therapy consisting of an effective kidney-targeted drug delivery. Dove Medical Press 2018-06-19 /pmc/articles/PMC6016261/ /pubmed/29950832 http://dx.doi.org/10.2147/IJN.S166445 Text en © 2018 Chen 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 Chen, Danfei Han, Shunping Zhu, Yongqin Hu, Fang Wei, Yinghui Wang, Guowei Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy therapy |
title | Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy therapy |
title_full | Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy therapy |
title_fullStr | Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy therapy |
title_full_unstemmed | Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy therapy |
title_short | Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy therapy |
title_sort | kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethylenimine nanoparticles for diabetic nephropathy therapy |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016261/ https://www.ncbi.nlm.nih.gov/pubmed/29950832 http://dx.doi.org/10.2147/IJN.S166445 |
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