Self-assembled nanoparticles based on chondroitin sulfate-deoxycholic acid conjugates for docetaxel delivery: Effect of degree of substitution of deoxycholic acid

Colloids Surf B Biointerfaces. 2016 Oct 1:146:235-44. doi: 10.1016/j.colsurfb.2016.06.019. Epub 2016 Jun 14.

Abstract

Hydrophobically-modified polymers based on chondroitin sulfate with different degree of substitution (DS) of deoxycholic acid (DOCA) were developed for docetaxel delivery. Chondroitin sulfate-deoxycholic acid (CSAD) bioconjugates were synthesized via the linker of adipic dihydrazide by amide bond. They were characterized with spherical shape, mean diameter of around 165.2nm and negative zeta potential (-14.87 to -20.53mV). An increase of DOCA DS reduced size of nanoparticles, while increasing drug loading efficiency. Drug release in vitro showed a triphasic sustained pattern and higher accumulative drug release percentage was observed with increased DS of DOCA on polymer. Self-assemblies with higher DS also had enhanced internalization of nanoparticles and stronger cytotoxicity at the cellular level. The self-assemble nanoparticles demonstrate to be excellent targeting drug delivery systems and the desired therapeutics can be achieved via the alteration of DS.

Keywords: CD44 receptor; Chondroitin sulfate; Degree of substitution; Docetaxel; Nanoparticles; Self-assembly.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Chondroitin Sulfates / chemistry*
  • Deoxycholic Acid / chemistry*
  • Docetaxel
  • Drug Carriers / chemistry*
  • Drug Delivery Systems*
  • Drug Liberation
  • Female
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Nanoparticles / chemistry*
  • Polymers / chemistry
  • Taxoids / chemistry
  • Taxoids / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Polymers
  • Taxoids
  • Deoxycholic Acid
  • Docetaxel
  • Chondroitin Sulfates