Starch-based dual amphiphilic graft copolymer as a new pH-sensitive maltidrug co-delivery system

Int J Biol Macromol. 2018 Oct 15;118(Pt A):913-920. doi: 10.1016/j.ijbiomac.2018.06.156. Epub 2018 Jun 30.

Abstract

Amphiphilic dual graft copolymer composed of starch (St) as main chain, poly caprolactone (PCL) and poly (2-ethyl 2-oxazoline) (POX) as hydrophobic and hydrophilic side chains were synthesized and characterized successfully. Firstly, polycaprolactone with propargyl end group prepared and attached to the surface of azido starch (St-N3) which was prepared through incomplete azidation of starch tosylate, by click chemistry reaction. Thereafter, the polymerization of 2-ethyl-2-oxazoline initiated from the remaining tosyl groups of PCL-starch. Finally, polymerization of POX quenched by doxorubicin (DOX) as anticancer drug as well as terminator and curcumin (Cur) physically loaded in to the obtained copolymer. Dual graft copolymer (PCL-St-POX) as the co-delivery system containing covalently conjugated doxorubicin and non-covalently loaded curcumin could be promising biocompatible system to achieve combination therapy. The SEM images showed that resulting copolymer exhibited sphere-shaped particles ranging from 50 to 100 nm which is completely different from ungrafted starch. The release studies also revealed that obtained copolymer is pH-sensitive and the release rate was more favorable at acidic pH (tumor cells) than neutral pH (normal cells) for both drugs.

Keywords: Amphiphilic polymers; Drug carrier; Dual graft copolymer; Starch.

MeSH terms

  • Antibiotics, Antineoplastic* / chemistry
  • Antibiotics, Antineoplastic* / pharmacokinetics
  • Antibiotics, Antineoplastic* / pharmacology
  • Curcumin* / chemistry
  • Curcumin* / pharmacokinetics
  • Curcumin* / pharmacology
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • Hydrogen-Ion Concentration
  • Nanospheres / chemistry*
  • Polyesters / chemistry
  • Starch* / chemistry
  • Starch* / pharmacokinetics
  • Starch* / pharmacology

Substances

  • Antibiotics, Antineoplastic
  • Delayed-Action Preparations
  • Polyesters
  • polycaprolactone
  • Doxorubicin
  • Starch
  • Curcumin