Oxidized polysaccharides for anticancer-drug delivery: What is the role of structure?

Carbohydr Polym. 2021 Apr 1:257:117562. doi: 10.1016/j.carbpol.2020.117562. Epub 2020 Dec 28.

Abstract

Study provides an in-depth analysis of the structure-function relationship of polysaccharide anticancer drug carriers and points out benefits and potential drawbacks of differences in polysaccharide glycosidic bonding, branching and drug binding mode of the carriers. Cellulose, dextrin, dextran and hyaluronic acid have been regioselectively oxidized to respective dicarboxylated derivatives, allowing them to directly conjugate cisplatin, while preserving their major structural features intact. The structure of source polysaccharide has crucial impact on conjugation effectiveness, carrier capacity, drug release rates, in vitro cytotoxicity and cellular uptake. For example, while branched structure of dextrin-based carrier partially counter the undesirable initial burst release, it also attenuates the cellular uptake and the cytotoxicity of carried drug. Linear polysaccharides containing β-(1→4) glycosidic bonds and oxidized at C2 and C3 (cellulose and hyaluronate) have the best overall combination of structural features for improved drug delivery applications including potentiation of the cisplatin efficacy towards malignances.

Keywords: Cellulose; Dextran; Dextrin; Drug delivery; Selective oxidation; Sodium hyaluronate.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Cellulose / chemistry
  • Cisplatin / administration & dosage*
  • Dextrans / chemistry
  • Dextrins / chemistry
  • Drug Carriers*
  • Drug Delivery Systems*
  • Drug Liberation
  • Glycosides / chemistry
  • Humans
  • Hyaluronic Acid / chemistry
  • In Vitro Techniques
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Mice
  • NIH 3T3 Cells
  • Oxidation-Reduction
  • Oxygen / chemistry*
  • Platinum / chemistry
  • Polysaccharides / chemistry*

Substances

  • Antineoplastic Agents
  • Dextrans
  • Dextrins
  • Drug Carriers
  • Glycosides
  • Polysaccharides
  • Platinum
  • Cellulose
  • Hyaluronic Acid
  • Cisplatin
  • Oxygen