Journal article
Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice
American journal of physiology. Renal physiology, v 311(2), pp F362-F372
01 Aug 2016
PMID: 26962109
Featured in Collection : UN Sustainable Development Goals @ Drexel
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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Details
- Title
- Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice
- Creators
- Danielle E Soranno - University of Colorado BoulderChristopher B Rodell - University of PennsylvaniaChristopher Altmann - University of Colorado DenverJane Duplantis - University of Colorado BoulderAna Andres-Hernando - University of Colorado DenverJason A Burdick - University of PennsylvaniaSarah Faubel - University of Colorado Denver
- Publication Details
- American journal of physiology. Renal physiology, v 311(2), pp F362-F372
- Publisher
- American Physiological Society (APS)
- Grant note
- UL1 TR001082 / NCATS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000384976500014
- Scopus ID
- 2-s2.0-84984666486
- Other Identifier
- 991019176801304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Physiology
- Urology & Nephrology