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      Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice

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          Abstract

          Injectable hydrogels can be used to deliver drugs in situ over a sustained period of time. We hypothesized that sustained delivery of interleukin-10 (IL-10) following acute kidney injury (AKI) would mitigate the local and systemic proinflammatory cascade induced by AKI and reduce subsequent fibrosis. Wild-type C57BL/6 mice underwent ischemia-reperfusion AKI with avertin anesthesia. Three days later, mice were treated with either hyaluronic acid injectable hydrogel with or without IL-10, or IL-10 suspended in saline, injected under the capsule of the left kidney, or hydrogel with IL-10 injected subcutaneously. Untreated AKI served as controls. Serial in vivo optical imaging tracked the location and degradation of the hydrogel over time. Kidney function was assessed serially. Animals were killed 28 days following AKI and the following were evaluated: serum IL-6, lung inflammation, urine neutrophil gelatinase-associated lipocalin, and renal histology for fibroblast activity, collagen type III deposition and fibrosis via Picrosirius Red staining and second harmonic imaging. Our model shows persistent systemic inflammation, and renal inflammation and fibrosis 28 days following AKI. The hydrogels are biocompatible and reduced serum IL-6 and renal collagen type III 28 days following AKI even when delivered without IL-10. Treatment with IL-10 reduced renal and systemic inflammation, regardless of whether the IL-10 was delivered in a sustained manner via the injectable hydrogel under the left kidney capsule, as a bolus injection via saline under the left kidney capsule, or via the injectable hydrogel subcutaneously. Injectable hydrogels are suitable for local drug delivery following renal injury, are biocompatible, and help mitigate local and systemic inflammation.

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          Author and article information

          Journal
          Am J Physiol Renal Physiol
          Am. J. Physiol. Renal Physiol
          ajprenal
          ajprenal
          AJPRENAL
          American Journal of Physiology - Renal Physiology
          American Physiological Society (Bethesda, MD )
          1931-857X
          1522-1466
          9 March 2016
          1 August 2016
          1 August 2017
          : 311
          : 2
          : F362-F372
          Affiliations
          [1] 1Departments of Pediatrics and Bioengineering, University of Colorado, Aurora, Colorado;
          [2] 2Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania; and
          [3] 3Department of Medicine, University of Colorado, Aurora, Colorado
          Author notes
          Address for reprint requests and other correspondence: D. E. Soranno, 13123 E. 16th Ave., Box 328 Aurora, CO 80045 (e-mail: Danielle.Soranno@ 123456childrenscolorado.org ).
          Article
          PMC5008670 PMC5008670 5008670 F-00579-2015
          10.1152/ajprenal.00579.2015
          5008670
          26962109
          f5c13db4-c21c-4ad1-bb90-1b4300093b42
          Copyright © 2016 the American Physiological Society
          History
          : 16 December 2015
          : 2 March 2016
          Funding
          Funded by: Research Institute, Children's Hospital Colorado
          Award ID: RSA Soranno
          Categories
          Articles

          chronic kidney disease,acute kidney injury,hyaluronic acid,injectable hydrogels,interleukin-10

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