title: Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice.
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.
authors.affiliation: Departments of Pediatrics and Bioengineering, University of Colorado, Aurora, Colorado; Danielle.Soranno@childrenscolorado.org.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Soranno
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Rodell
authors.affiliation: Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Christopher
authors.initials: C
authors.lastname: Altmann
authors.affiliation: Departments of Pediatrics and Bioengineering, University of Colorado, Aurora, Colorado;
authors.forename: Jane
authors.initials: J
authors.lastname: Duplantis
authors.affiliation: Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Ana
authors.initials: A
authors.lastname: Andres-Hernando
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
authors.affiliation: Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Sarah
authors.initials: S
authors.lastname: Faubel
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000818:Animals; D016503:Drug Delivery Systems; D005355:Fibrosis; D006820:Hyaluronic Acid; D020100:Hydrogels; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D000071068:Lipocalin-2 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D020100:Hydrogels; D015850:Interleukin-6; D000071068:Lipocalin-2; C577686:interleukin-6, mouse; C071332:Lcn2 protein, mouse; D016753:Interleukin-10; D006820:Hyaluronic Acid
keywords: acute kidney injury; chronic kidney disease; hyaluronic acid; injectable hydrogels; interleukin-10