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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-06-01
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| Series: | International Journal of Nanomedicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/kidney-targeted-drug-delivery-via-rhein-loaded-polyethyleneglycol-co-p-peer-reviewed-article-IJN |
| _version_ | 1818854087934869504 |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-19T07:47:08Z |
| format | Article |
| id | doaj.art-f5186f17bf634bffbc64b55599079c11 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-19T07:47:08Z |
| publishDate | 2018-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-f5186f17bf634bffbc64b55599079c112022-12-21T20:30:17ZengDove Medical PressInternational Journal of Nanomedicine1178-20132018-06-01Volume 133507352738899Kidney-targeted drug delivery via rhein-loaded polyethyleneglycol-co-polycaprolactone-co-polyethyleneimine nanoparticles for diabetic nephropathy therapyChen DFHan SPZhu YQHu FWei YHWang GWDanfei 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 deliveryhttps://www.dovepress.com/kidney-targeted-drug-delivery-via-rhein-loaded-polyethyleneglycol-co-p-peer-reviewed-article-IJNRheinDiabetic NephropathyPolyethyleneglycol-co-polycaprolactone -co-polyethyleneimineNanoparticlesIn vitro/vivo EvaluationTargeting Drug Delivery |
| spellingShingle | 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 International Journal of Nanomedicine Rhein Diabetic Nephropathy Polyethyleneglycol-co-polycaprolactone -co-polyethyleneimine Nanoparticles In vitro/vivo Evaluation Targeting Drug Delivery |
| title | 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_short | 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 |
| topic | Rhein Diabetic Nephropathy Polyethyleneglycol-co-polycaprolactone -co-polyethyleneimine Nanoparticles In vitro/vivo Evaluation Targeting Drug Delivery |
| url | https://www.dovepress.com/kidney-targeted-drug-delivery-via-rhein-loaded-polyethyleneglycol-co-p-peer-reviewed-article-IJN |
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