Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy

Danfei Chen,1 Shunping Han,2,3 Yongqin Zhu,1 Fang Hu,1 Yinghui Wei,3 Guowei Wang3,4 1Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 China; 2Department of Chemistry, Imperial College London, London, UK; 3College of Pharmaceutical Scie...

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Autores principales:	Chen DF, Han SP, Zhu YQ, Hu F, Wei YH, Wang GW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Rhein Diabetic Nephropathy Polyethyleneglycol-co-polycaprolactone -co-polyethyleneimine Nanoparticles In vitro/vivo Evaluation Targeting Drug Delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f5186f17bf634bffbc64b55599079c11
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spelling	oai:doaj.org-article:f5186f17bf634bffbc64b55599079c112021-12-02T08:11:07ZKidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy1178-2013https://doaj.org/article/f5186f17bf634bffbc64b55599079c112018-06-01T00:00:00Zhttps://www.dovepress.com/kidney-targeted-drug-delivery-via-rhein-loaded-polyethyleneglycol-co-p-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Danfei Chen,1 Shunping Han,2,3 Yongqin Zhu,1 Fang Hu,1 Yinghui Wei,3 Guowei Wang3,4 1Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 China; 2Department of Chemistry, Imperial College London, London, UK; 3College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053 China; 4College of Biological and Chemical Engineering, Zhejiang University, Hangzhou, 310007 China 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. Keywords: rhein, diabetic nephropathy, polyethyleneglycol-co-polycaprolactone-co- polyethylenimine, nanoparticles, in vitro/vivo evaluation, targeting drug deliveryChen DFHan SPZhu YQHu FWei YHWang GWDove Medical PressarticleRheinDiabetic NephropathyPolyethyleneglycol-co-polycaprolactone -co-polyethyleneimineNanoparticlesIn vitro/vivo EvaluationTargeting Drug DeliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3507-3527 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Rhein Diabetic Nephropathy Polyethyleneglycol-co-polycaprolactone -co-polyethyleneimine Nanoparticles In vitro/vivo Evaluation Targeting Drug Delivery Medicine (General) R5-920
spellingShingle	Rhein Diabetic Nephropathy Polyethyleneglycol-co-polycaprolactone -co-polyethyleneimine Nanoparticles In vitro/vivo Evaluation Targeting Drug Delivery Medicine (General) R5-920 Chen DF Han SP Zhu YQ Hu F Wei YH Wang GW Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy
description	Danfei Chen,1 Shunping Han,2,3 Yongqin Zhu,1 Fang Hu,1 Yinghui Wei,3 Guowei Wang3,4 1Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 China; 2Department of Chemistry, Imperial College London, London, UK; 3College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053 China; 4College of Biological and Chemical Engineering, Zhejiang University, Hangzhou, 310007 China 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. Keywords: rhein, diabetic nephropathy, polyethyleneglycol-co-polycaprolactone-co- polyethylenimine, nanoparticles, in vitro/vivo evaluation, targeting drug delivery
format	article
author	Chen DF Han SP Zhu YQ Hu F Wei YH Wang GW
author_facet	Chen DF Han SP Zhu YQ Hu F Wei YH Wang GW
author_sort	Chen DF
title	Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy
title_short	Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy
title_full	Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy
title_fullStr	Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy
title_full_unstemmed	Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy
title_sort	kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/f5186f17bf634bffbc64b55599079c11
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Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapy

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