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

Sok Bee Lim, Israel Rubinstein, Ruxana T. Sadikot, James E. Artwohl, Hayat Önyüksel

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)662-672
Number of pages11
JournalPharmaceutical Research
Volume28
Issue number3
DOIs
StatePublished - Mar 2011
Externally publishedYes

Keywords

  • GLP-1
  • PEGylated phospholipid micelles
  • acute lung injury
  • anti-inflammation
  • gram-negative sepsis

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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