PMID- 23913854 OWN - NLM STAT- MEDLINE DCOM- 20150112 LR - 20211021 IS - 1552-4965 (Electronic) IS - 1549-3296 (Print) IS - 1549-3296 (Linking) VI - 102 IP - 7 DP - 2014 Jul TI - Immunotherapy with injectable hydrogels to treat obstructive nephropathy. PG - 2173-80 LID - 10.1002/jbm.a.34902 [doi] AB - Hydrogels are gaining attention as injectable vehicles for delivery of therapeutics for a range of applications. We describe self-assembling and injectable Dock-and-Lock hydrogels for local delivery of interleukin-10 (IL-10) to abate the progression of inflammation and fibrosis that leads to chronic kidney disease. As monitored with a fluorescent tag, hydrogels degraded within a few days in vitro and matched IL-10 release profiles; however, hydrogels remained in the kidney for up to 30 days in vivo. A unilateral ureteral obstruction (UUO) mouse model was used to investigate in vivo outcomes after hydrogel injection and IL-10 delivery. Eight groups were investigated (7, 21, 35 days, n = 4): healthy, sham, healthy injected with mouse serum albumin (MSA), healthy + hydrogel, UUO, UUO + IL-10, UUO + hydrogel, UUO + hydrogel/IL-10. 15 muL of IL-10, hydrogel, or hydrogel/IL-10 was injected under the renal capsule 3 days after the UUO. Immunohistochemistry (IHC) was performed on paraffin sections to identify macrophages and apoptotic cells and trichrome staining was used to evaluate fibrosis. There were no significant differences in inflammatory markers between all control groups. With hydrogel delivery, macrophage infiltration and apoptosis were significantly reduced at days 21 and 35 compared to untreated animals. By day 35, IL-10 delivery via hydrogel reduced macrophage infiltration and apoptosis more than IL-10 injection alone. Fibrosis was decreased by day 35 in all treatment groups. This work supports the use of hydrogel delivery of IL-10 to treat chronic kidney disease. CI - (c) 2013 Wiley Periodicals, Inc. FAU - Soranno, Danielle E AU - Soranno DE AD - Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Lu, Hoang D AU - Lu HD FAU - Weber, Heather M AU - Weber HM FAU - Rai, Reena AU - Rai R FAU - Burdick, Jason A AU - Burdick JA LA - eng GR - T32 DK007378/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20130808 PL - United States TA - J Biomed Mater Res A JT - Journal of biomedical materials research. Part A JID - 101234237 RN - 0 (Hydrogels) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Apoptosis MH - Disease Models, Animal MH - *Hydrogels MH - *Immunotherapy MH - Interleukin-10/metabolism MH - Kidney Diseases/metabolism/pathology/*therapy MH - Macrophages/cytology MH - Mice MH - Mice, Inbred BALB C PMC - PMC3928238 MID - NIHMS547284 OTO - NOTNLM OT - drug delivery OT - hydrogel OT - inflammation OT - kidney OT - nephropathy EDAT- 2013/08/06 06:00 MHDA- 2015/01/13 06:00 PMCR- 2015/07/01 CRDT- 2013/08/06 06:00 PHST- 2013/06/29 00:00 [received] PHST- 2013/07/25 00:00 [accepted] PHST- 2013/08/06 06:00 [entrez] PHST- 2013/08/06 06:00 [pubmed] PHST- 2015/01/13 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] AID - 10.1002/jbm.a.34902 [doi] PST - ppublish SO - J Biomed Mater Res A. 2014 Jul;102(7):2173-80. doi: 10.1002/jbm.a.34902. Epub 2013 Aug 8.