Journal article
Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles
Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women’s Hospital1
Departments of Medicine, Pathology and Cell Biology, and Physiology2
Translational and Molecular Imaging Institute3
Department of Chemical Engineering4
Excessive inflammation and failed resolution of the inflammatory response are underlying components of numerous conditions such as arthritis, cardiovascular disease, and cancer. Hence, therapeutics that dampen inflammation and enhance resolution are of considerable interest. In this study, we demonstrate the proresolving activity of sub–100-nm nanoparticles (NPs) containing the anti-inflammatory peptide Ac2-26, an annexin A1/lipocortin 1-mimetic peptide.
These NPs were engineered using biodegradable diblock poly(lactic-co-glycolic acid)-b-polyethyleneglycol and poly(lactic-co-glycolic acid)-b-polyethyleneglycol collagen IV–targeted polymers. Using a self-limited zymosan-induced peritonitis model, we show that the Ac2-26 NPs (100 ng per mouse) were significantly more potent than Ac2-26 native peptide at limiting recruitment of polymononuclear neutrophils (56% vs. 30%) and at decreasing the resolution interval up to 4 h.
Moreover, systemic administration of collagen IV targeted Ac2-26 NPs (in as low as 1 µg peptide per mouse) was shown to significantly block tissue damage in hind-limb ischemia-reperfusion injury by up to 30% in comparison with controls. Together, these findings demonstrate that Ac2-26 NPs are proresolving in vivo and raise the prospect of their use in chronic inflammatory diseases such as atherosclerosis.
Language: | Undetermined |
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Publisher: | National Academy of Sciences |
Year: | 2013 |
Pages: | 6506-6511 |
ISSN: | 10916490 and 00278424 |
Types: | Journal article |
DOI: | 10.1073/pnas.1303377110 |
Analysis of Variance Animals Annexin A1 Collagen Type IV Female Flow Cytometry Hindlimb Kinetics Mice Mice, Inbred C57BL Nanoparticles Nanotechnology Neutrophils Peptides Peritonitis Reperfusion Injury annexin A1 peptide (2-26) controlled release inflammation resolution nanomedicine nanotechnology