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Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles.


ABSTRACT: 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.

SUBMITTER: Kamaly N 

PROVIDER: S-EPMC3631648 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles.

Kamaly Nazila N   Fredman Gabrielle G   Subramanian Manikandan M   Gadde Suresh S   Pesic Aleksandar A   Cheung Louis L   Fayad Zahi Adel ZA   Langer Robert R   Tabas Ira I   Farokhzad Omid Cameron OC  

Proceedings of the National Academy of Sciences of the United States of America 20130326 16


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 biodegrad  ...[more]

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