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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...

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Autores principales: Chen, Danfei, Han, Shunping, Zhu, Yongqin, Hu, Fang, Wei, Yinghui, Wang, Guowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
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.
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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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