Design and evaluation of a novel potential carrier for a hydrophilic antitumor drug: Auricularia auricular polysaccharide-chitosan nanoparticles as a delivery system for doxorubicin hydrochloride

Int J Pharm. 2016 Sep 10;511(1):267-275. doi: 10.1016/j.ijpharm.2016.07.026. Epub 2016 Jul 14.

Abstract

To improve the low loading content of hydrophilic drugs in nanodrug delivery systems, a natural watersoluble polysaccharide, Auricularia auricular polysaccharide (AAP), was extracted and purified as a vehicle for the hydrophilic drug doxorubicin hydrochloride (Dox·HCl). This involved the preparation of polyelectrolyte complexes nanoparticles (PEC NPs) using the electrostatic interaction between cationic chitosan (CS) and anionic AAP. The formation of AAP-CS-NPs was confirmed by FT-IR and TEM. It was found that Dox-loaded AAP-CS-NPs possessed a spherical morphology with average diameters of 237.6nm and 74.1% Dox·HCl encapsulation efficiency. The stability of Dox AAP-CS-NPs was examined by suspending the nanoparticles in PBS (pH 7.4) at room temperature. The particle size of the nanoparticle samples remained stable and exhibited no obvious variations in drug content after half a month. In addition, in vitro cytotoxicity studies showed that blank AAP-CS-NPs did not exhibit any cytotoxic effects, while Dox AAP-CS-NPs increased the Dox·HCl cytotoxicity against MCF-7 cells as the result of significantly increased cellular uptake, compared with free Dox·HCl. Hence, the overall results obtained suggest that AAP-CS-NPs are very effective in entrapping Dox·HCl and to penetrate into tumor cells, rendering them promising carriers for hydrophilic antitumor drugs.

Keywords: Auricularia auricular polysaccharide; Chitosan; Doxorubicin hydrochloride; Hydrophilic; Nanoparticles.

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / isolation & purification
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Chitosan / administration & dosage*
  • Chitosan / isolation & purification
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage*
  • Drug Carriers / administration & dosage
  • Drug Carriers / isolation & purification
  • Drug Delivery Systems / methods*
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • MCF-7 Cells
  • Nanoparticles / administration & dosage*
  • Polysaccharides / administration & dosage*
  • Polysaccharides / isolation & purification

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Polysaccharides
  • Doxorubicin
  • Chitosan