Formulation and optimization of oxaliplatin immuno-nanoparticles using Box-Behnken design and cytotoxicity assessment for synergistic and receptor-mediated targeting in the treatment of colorectal cancer

Artif Cells Nanomed Biotechnol. 2016 Dec;44(8):1835-1850. doi: 10.3109/21691401.2015.1111226. Epub 2015 Dec 24.

Abstract

Conventional chemotherapy majorly lacks clinical application attributed to its inspecificity, adverse effects and inability to penetrate into tumor cells. Hence, the aim of the study was to prepare oxaliplatin solid lipid nanoparticles (OP-SLN) by microemulsion method optimizing it by Box-Behnken design and then covalently conjugated to TRAIL (CD-253) monoclonal antibody (TR-OP-SLN) for targeting colorectal cancer cells. The optimized OP-SLN3 has shown an appreciable particle size (121 ± 1.22 nm), entrapment efficiency (78 ± 0.09%) and drug loading (32 ± 1.01%). Fluorescence study and the Bradford assay further confirmed the binding of the protein. A 1.5-fold increase in cytotoxicity of immuno-nanoparticles (4.9 μM) was observed.

Keywords: Box–Behnken; immuno-nanoparticles; oxaliplatin; site-specificity.

MeSH terms

  • Antibodies, Monoclonal* / chemistry
  • Antibodies, Monoclonal* / pharmacokinetics
  • Antibodies, Monoclonal* / pharmacology
  • Antibodies, Neoplasm* / chemistry
  • Antibodies, Neoplasm* / pharmacology
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Cytotoxins* / chemistry
  • Cytotoxins* / pharmacokinetics
  • Cytotoxins* / pharmacology
  • Drug Delivery Systems / methods*
  • Humans
  • Nanoparticles / chemistry*
  • Organoplatinum Compounds* / chemistry
  • Organoplatinum Compounds* / pharmacokinetics
  • Organoplatinum Compounds* / pharmacology
  • Oxaliplatin
  • TNF-Related Apoptosis-Inducing Ligand*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Cytotoxins
  • Organoplatinum Compounds
  • TNF-Related Apoptosis-Inducing Ligand
  • Oxaliplatin