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Composition-dependent structural changes and antitumor activity of ASC-DP/DSPE-PEG nanoparticles.

Kenjirou Higashi1, Fusako Mibu1, Kengo Saito2

  • 1Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|December 6, 2016
PubMed
Summary

Stable nanoparticles were created using Ascorbyl 2,6-dipalmitate (ASC-DP) and DSPE-PEG. These nanoparticles show tumor cell-specific cytotoxicity, making them promising for cancer therapy.

Keywords:
Ascorbyl 2,6-dipalmitateCytotoxicityDSPE-PEGDiskNanoparticlesTube

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Area of Science:

  • Nanotechnology
  • Materials Science
  • Biochemistry

Background:

  • Ascorbyl 2,6-dipalmitate (ASC-DP) is a vitamin C derivative with potential anticancer properties.
  • Distearoyl phosphatidylethanolamine polyethylene glycol 2000 (DSPE-PEG) is a common lipid-based excipient used for nanoparticle formulation.

Purpose of the Study:

  • To develop and characterize stable nanoparticles using ASC-DP and DSPE-PEG.
  • To investigate the structure and properties of these nanoparticles.
  • To evaluate the in vitro cytotoxicity of ASC-DP/DSPE-PEG nanoparticles against cancer cells.

Main Methods:

  • Nanoparticle formation via solvent-evaporated film dispersion in water.
  • Particle size analysis using dynamic light scattering (DLS).
  • Molecular state analysis using wide-angle X-ray diffraction (WAXD), infrared (IR), and solid-state nuclear magnetic resonance (NMR) spectroscopy.
  • Nanoparticle morphology investigation using transmission electron microscopy (TEM).
  • Structural elucidation in solution using quantitative solution-state 1H NMR.
  • Cytotoxicity assays on cancer and normal cell lines.

Main Results:

  • Stable ASC-DP/DSPE-PEG nanoparticles (100-160nm) were formed at ASC-DP:DSPE-PEG molar ratios ≤ 2:1.
  • Nanoparticle morphology transitioned from micelle to disk and tubular structures with increasing ASC-DP ratio.
  • Solution-state NMR revealed a core-shell structure with ASC-DP and DSPE hydrophobic chains forming the core and PEG chains forming the hydrophilic shell.
  • ASC-DP/DSPE-PEG nanoparticles exhibited specific cytotoxicity against cancer cell lines with no observed toxicity against normal cells.

Conclusions:

  • The ASC-DP/DSPE-PEG formulation yields stable nanoparticles with a defined core-shell structure.
  • The nanoparticles demonstrate tumor cell-specific cytotoxicity.
  • This formulation holds potential for cancer monotherapy or combination therapy.