Self-assembled nanoparticles based on glycol chitosan bearing 5beta-cholanic acid for RGD peptide delivery

J Control Release. 2004 Mar 24;95(3):579-88. doi: 10.1016/j.jconrel.2003.12.020.

Abstract

The synthetic peptide bearing Arg-Gly-Asp (RGD) sequence is considered to specifically bind to alpha(v)beta(3) integrin expressed on endothelial cells in the angiogenic blood vessels, which provides a potential to inhibit the tumor growth. As a carrier for the RGD peptide, hydrophobically modified glycol chitosan (HGC) capable of forming nano-sized self-aggregates was prepared by the chemical conjugation of 5beta-cholanic acid to the main backbone of glycol chitosan. The RGD peptide labeled with fluoresein isothiocyanate (FITC-GRGDS) was loaded into self-aggregates in three different conditions: simple mixing, sonication, and solvent evaporation methods. Of different methods applied, solvent evaporation method showed the most promising results for peptide loading, as judged by the yield (>70%) and loading efficiency (>75%). It was found that the presence of FITC-labeled peptides makes the self-aggregates to be compact, possibly due to the role of both hydrophobic FITC and peptides containing carboxylic acids that allow hydrogen bonding and electrostatic interaction with the primary amino groups in the main backbone of glycol chitosan. FITC-labeled peptides were released from self-aggregates in a physiological solution (pH 7.4) for up to 1 day. From the cell adhesion and migration assays, it was demonstrated that FITC labeling of peptides does not significantly deteriorate biological activity of the parent peptide drug (GRGDS). Overall, the self-aggregates loaded with FITC-GRGDS might be useful for monitoring or destroying the angiogenic vessels surrounding the tumor tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / therapeutic use
  • Chitosan / chemical synthesis
  • Chitosan / metabolism*
  • Cholanes / chemistry
  • Cholanes / metabolism*
  • Cholic Acids / chemistry
  • Cholic Acids / metabolism*
  • Drug Carriers / chemistry
  • Drug Carriers / therapeutic use
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Fluorescein-5-isothiocyanate / chemistry
  • Fluorescein-5-isothiocyanate / metabolism
  • Humans
  • Integrin alphaVbeta3 / genetics
  • Integrin alphaVbeta3 / metabolism
  • Methods
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Oligopeptides / therapeutic use*
  • Particle Size*
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects

Substances

  • Angiogenesis Inhibitors
  • Cholanes
  • Cholic Acids
  • Drug Carriers
  • Integrin alphaVbeta3
  • Oligopeptides
  • glycol-chitosan
  • arginyl-glycyl-aspartic acid
  • Chitosan
  • Fluorescein-5-isothiocyanate
  • cholanic acid