Cyclic nigerosyl-1,6-nigerose-based nanosponges: An innovative pH and time-controlled nanocarrier for improving cancer treatment

Carbohydr Polym. 2018 Aug 15:194:111-121. doi: 10.1016/j.carbpol.2018.04.027. Epub 2018 Apr 6.

Abstract

The design and structural optimisation of a novel polysaccharide-based nanomaterial for the controlled and sustained release of doxorubicin are here reported. A cross-linked polymer was obtained by reacting a tetraglucose, named cyclic nigerosyl-1-6-nigerose (CNN), with pyromellitic dianhydride. The cross-linking reaction formed solid nanoparticles, named nanosponges, able to swell as a function of the pH. Nanoparticle sizes were reduced using High Pressure Homogenization, to obtain uniform nanosuspensions. Doxorubicin was incorporated into the CNN-nanosponges in a good extent. DSC and solid state NMR analyses proved the drug interaction with the polymer matrix. In vitro studies demonstrated pH-dependent slow and prolonged release kinetics of the drug from the nanoformulation. Doxorubicin-loaded CNN-nanosponges were easily internalized in A2780 cell line. They might considered an intracellular doxorubicin reservoir, able to slowly release the drug over time. CNN-nanosponges may be promising biocompatible nanocarriers for the sustained delivery of doxorubicin with potential localised application in cancer treatments.

Keywords: CNN; Doxorubicin; Nanosponges; Nigerose; Sustained release.

MeSH terms

  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Benzoates / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cross-Linking Reagents / chemistry
  • Disaccharidases / chemistry*
  • Dose-Response Relationship, Drug
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers / chemistry
  • Drug Screening Assays, Antitumor
  • Humans
  • Hydrogen-Ion Concentration
  • Nanostructures / chemistry*
  • Particle Size
  • Structure-Activity Relationship
  • Surface Properties
  • Time Factors

Substances

  • Antibiotics, Antineoplastic
  • Benzoates
  • Cross-Linking Reagents
  • Drug Carriers
  • pyromellitic dianhydride
  • Doxorubicin
  • Disaccharidases