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Determinants of preferential renal accumulation of synthetic polymers in acute kidney injury.

Authors
  • Chen, Yi1
  • Tang, Weimin1
  • Yu, Fei1
  • Xie, Ying1
  • Jaramillo, Lee1
  • Jang, Hee-Seong2
  • Li, Jing1
  • Padanilam, Babu J3
  • Oupický, David4
  • 1 Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • 2 Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • 3 Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Internal Medicine, Section of Nephrology, University of Nebraska Medical Center, Omaha, NE, USA.
  • 4 Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: [email protected]
Type
Published Article
Journal
International journal of pharmaceutics
Publication Date
Jul 22, 2019
Volume
568
Pages
118555–118555
Identifiers
DOI: 10.1016/j.ijpharm.2019.118555
PMID: 31344445
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Acute kidney injury (AKI) is a major kidney disease associated with high mortality and morbidity. AKI may lead to chronic kidney disease and end-stage renal disease. Currently, the management of AKI is mainly focused on supportive treatments. Previous studies showed macromolecular delivery systems as a promising method to target AKI, but little is known about how physicochemical properties affect the renal accumulation of polymers in ischemia-reperfusion AKI. In this study, a panel of fluorescently labeled polymers with a range of molecular weights and net charge was synthesized by living radical polymerization. By testing biodistribution of the polymers in unilateral ischemia-reperfusion mouse model of AKI, the results showed that negatively charged and neutral polymers had the greatest potential for selectively accumulating in I/R kidneys. The polymers passed through glomerulus and were retained in proximal tubular cells for up to 24 h after injection. The results obtained in the unilateral model were validated in a bilateral ischemic-reperfusion model. This study demonstrates for the first time that polymers with specific physicochemical characteristics exhibit promising ability to accumulate in the injured AKI kidney, providing initial insights on their use as polymeric drug delivery systems in AKI. Copyright © 2019 Elsevier B.V. All rights reserved.

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