Peptide conjugated polymeric nanoparticles as a carrier for targeted delivery of docetaxel

Colloids Surf B Biointerfaces. 2014 May 1:117:166-73. doi: 10.1016/j.colsurfb.2014.02.026. Epub 2014 Feb 23.

Abstract

The aim of this research work was to develop Bombesin peptide (BBN) conjugated, docetaxel loaded nanocarrier for the treatment of breast cancer. Docetaxel loaded nanoparticles (DNP) were prepared by solvent evaporation method using sodium cholate as surfactant. BBN was conjugated to DNP surface through covalent bonding. Both DNP and BBN conjugated DNP (BDNP) were characterized by various techniques such as dynamic light scattering, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis. The particle diameter and zeta potential of BDNP were 136±3.95 nm and -10.8±2.7 mV, respectively. The change in surface charge and FTIR studies confirmed the formation of amide linkage between BBN and DNP. AFM analysis showed that nanoparticles were spherical in shapes. In nanoparticles, docetaxel was present in its amorphous form as confirmed by DSC and PXRD analysis and was stable during the thermal studies. The formulations showed the sustained release of DTX over the period of 120 h. During cellular toxicity assay in gastrin releasing peptide receptor positive breast cancer cells (MDA-MB-231), BDNP were found to be 12 times more toxic than pure DTX and Taxotere. The IC50 value for DTX, Taxotere, DNP and BDNP was >375, >375, 142.23 and 35.53 ng/ml, respectively. The above studies showed that Bombesin conjugated nanocarrier system could be a promising carrier for active targeting of anticancer drugs in GRP receptor over expressing cancer cells.

Keywords: Bombesin; Breast cancer; Conjugation; Docetaxel; Nanoparticles; Targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bombesin / chemistry*
  • Calorimetry, Differential Scanning
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Docetaxel
  • Drug Carriers / chemistry*
  • Drug Delivery Systems*
  • Humans
  • Lactic Acid / chemistry*
  • Nanoparticles / chemistry*
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Spectroscopy, Fourier Transform Infrared
  • Taxoids / pharmacology*
  • Thermogravimetry
  • X-Ray Diffraction

Substances

  • Drug Carriers
  • Taxoids
  • Docetaxel
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Bombesin