Biological characterization of a novel hybrid copolymer carrier system based on glycogen

Drug Deliv Transl Res. 2018 Feb;8(1):73-82. doi: 10.1007/s13346-017-0436-x.

Abstract

The effective drug delivery systems for cancer treatment are currently on high demand. In this paper, biological behavior of the novel hybrid copolymers based on polysaccharide glycogen were characterized. The copolymers were modified by fluorescent dyes for flow cytometry, confocal microscopy, and in vivo fluorescence imaging. Moreover, the effect of oxazoline grafts on degradation rate was examined. Intracellular localization, cytotoxicity, and internalization route of the modified copolymers were examined on HepG2 cell line. Biodistribution of copolymers was addressed by in vivo fluorescence imaging in C57BL/6 mice. Our results indicate biocompatibility, biodegradability, and non-toxicity of the glycogen-based hybrid copolymers. Copolymers were endocyted into the cytoplasm, most probably via caveolae-mediated endocytosis. Higher content of oxazoline in polymers slowed down cellular uptake. No strong colocalization of the glycogen-based probe with lysosomes was observed; thus, it seems that the modified externally administered glycogen is degraded in the same way as an endogenous glycogen. In vivo experiment showed relatively fast biodistribution and biodegradation. In conclusion, this novel nanoprobe offers unique chemical and biological attributes for its use as a novel drug delivery system that might serve as an efficient carrier for cancer therapeutics with multimodal imaging properties.

Keywords: Cancer; Contrast agents; Drug delivery; Glycogen; Polymers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Carriers / administration & dosage*
  • Drug Carriers / pharmacokinetics
  • Endocytosis
  • Fluorescein-5-isothiocyanate / administration & dosage
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Fluorescent Dyes / administration & dosage
  • Fluorescent Dyes / pharmacokinetics
  • Glycogen / administration & dosage*
  • Glycogen / pharmacokinetics
  • Hep G2 Cells
  • Heterocyclic Compounds / administration & dosage
  • Heterocyclic Compounds / pharmacokinetics
  • Humans
  • Mice, Inbred C57BL
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / pharmacokinetics
  • Polyamines / administration & dosage
  • Polyamines / pharmacokinetics
  • Tissue Distribution

Substances

  • Drug Carriers
  • Fluorescent Dyes
  • Heterocyclic Compounds
  • Organometallic Compounds
  • Polyamines
  • poly(2-methyl-2-oxazoline)
  • Glycogen
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
  • Fluorescein-5-isothiocyanate