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Pharm Res. 2011 Mar;28(3):662-72. doi: 10.1007/s11095-010-0322-4. Epub 2010 Nov 25.

A novel peptide nanomedicine against acute lung injury: GLP-1 in phospholipid micelles.

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  • 1Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.

Abstract

PURPOSE:

Treatment of acute lung injury (ALI) observed in Gram-negative sepsis represents an unmet medical need due to a high mortality rate and lack of effective treatment. Accordingly, we developed and characterized a novel nanomedicine against ALI. We showed that when human glucagon-like peptide 1(7-36) (GLP-1) self-associated with PEGylated phospholipid micelles (SSM), the resulting GLP1-SSM (hydrodynamic size, ~15 nm) exerted effective anti-inflammatory protection against lipopolysaccharide (LPS)-induced ALI in mice.

METHODS:

GLP1-SSM was prepared by incubating GLP-1 with SSM dispersion in saline and characterized using fluorescence spectroscopy and circular dichroism. Bioactivity was tested by in vitro cAMP induction, while in vivo anti-inflammatory effects were determined by lung neutrophil cell count, myeloperoxidase activity and pro-inflammatory cytokine levels in LPS-induced ALI mice.

RESULTS:

Amphipathic GLP-1 interacted spontaneously with SSM as indicated by increased α-helicity and fluorescence emission. This association elicited increased bioactivity as determined by in vitro cAMP production. Correspondingly, subcutaneous GLP1-SSM (5-30 nmol/mouse) manifested dose-dependent decrease in lung neutrophil influx, myeloperoxidase activity and interleukin-6 in ALI mice. By contrast, GLP-1 in saline showed no significant anti-inflammatory effects against LPS-induced lung hyper-inflammatory responses.

CONCLUSIONS:

GLP1-SSM is a promising novel anti-inflammatory nanomedicine against ALI and should be further developed for its transition to clinics.

PMID:
21108040
[PubMed - indexed for MEDLINE]
PMCID:
PMC3789646
Free PMC Article
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