Long-circulating poly(ethylene glycol)-grafted gelatin nanoparticles customized for intracellular delivery of noscapine: preparation, in-vitro characterization, structure elucidation, pharmacokinetics, and cytotoxicity analyses

Anticancer Drugs. 2011 Jul;22(6):543-55. doi: 10.1097/CAD.0b013e32834159b8.

Abstract

Noscapine, the tubulin-binding anticancer agent, when administered orally, requires high ED(50) (300-600 mg/kg), whereas intravenous administration (10 mg/kg) results in rapid elimination of the drug with a half-life of 0.39 h. Hence, the development of long-circulating injectable nanoparticles can be an interesting option for designing a viable formulation of noscapine for anticancer activity. Noscapine-enveloped gelatin nanoparticles and poly(ethylene glycol)-grafted gelatin nanoparticles were constructed and characterized. Data indicate that smooth and spherical shaped nanoparticles of 127 ± 15 nm were engineered with maximum entrapment efficiency of 65.32 ± 3.81%. Circular dichroism confirms that nanocoacervates retained the α-helical content of gelatin in ethanol whereas acetone favored the formation of a random coil. Moreover, the Fourier transform infrared and powder X-ray diffraction pattern prevents any significant change in the noscapine-loaded gelatin nanoparticles in comparison with individual components. In-vitro release kinetic data suggest a first-order release of noscapine (85.1%) from gelatin nanoparticles with a release rate constant of 7.611×10(-3). It is to be noted that there is a 1.43-fold increase in the area under the curve up to the last sampling point for the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles over the noscapine-loaded gelatin nanoparticles and a 13.09-fold increase over noscapine. Cytotoxicity analysis of the MCF-7 cell line indicated that the IC(50) value of the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles was equivalent to 20.8 μmol/l, which was significantly (P<0.05) lower than the IC(50) value of the noscapine-loaded gelatin nanoparticles (26.3 μmol/l) and noscapine (40.5 μmol/l).Noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles can be developed as a promising therapeutic agent for the management of breast cancer.

MeSH terms

  • Amines / chemistry
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Area Under Curve
  • Cell Line, Tumor
  • Circular Dichroism
  • Drug Compounding
  • Drug Delivery Systems / methods
  • Drug Stability
  • Electrochemistry
  • Excipients
  • Female
  • Gelatin
  • Humans
  • Mice
  • Microscopy, Atomic Force
  • Microscopy, Electron
  • Microscopy, Electron, Transmission
  • Nanoparticles* / chemistry
  • Noscapine / administration & dosage*
  • Noscapine / pharmacokinetics
  • Noscapine / pharmacology
  • Particle Size
  • Polyethylene Glycols
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Amines
  • Angiogenesis Inhibitors
  • Excipients
  • Polyethylene Glycols
  • Noscapine
  • Gelatin