A novel peptide nanomedicine against acute lung injury: GLP-1 in phospholipid micelles.
OBJECTIVE
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.
Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
Sok Bee
SB
Lim
Israel
I
Rubinstein
Ruxana T
RT
Sadikot
James E
JE
Artwohl
Hayat
H
Önyüksel
D055371:Acute Lung Injury / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D050997:Nanomedicine / Q000379:methods*; D010743:Phospholipids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats
D018836:Inflammation Mediators; D008823:Micelles; D010743:Phospholipids; D052216:Glucagon-Like Peptide 1