Biocompatibility studies of intravenously administered ionic-crosslinked chitosan-BSA nanoparticles as vehicles for antitumour drugs

Int J Pharm. 2019 Jan 10:554:337-351. doi: 10.1016/j.ijpharm.2018.11.027. Epub 2018 Nov 12.

Abstract

In this study, a new alternative of ionic crosslinked nanoparticles (NPs) based on chitosan (C) and bovine serum albumin (A; BSA) was evaluated as drug delivery system for antitumour compounds (doxorubicin hydrochloride as a model). The different responses to the pH of the medium were determined by the electrostatic interactions induced by each polymeric combination (C50/A50; C80/A20; C20/A80). NPs revealed a nanoscale size (167-392 nm) and a positive net charge (12-26 mV), modulated by doxorubicin (DOX) loading. Drug loading capacity was higher than 5.2 ± 1.8 μgDOX/mgNP (Encapsulation efficiency = 34%), and an initial burst release was followed by a sustained delivery. Cellular uptake assays confirmed the entry of NPs in three human tumor cells (MCF7, T47D and Hela), triggering antioxidant responses (superoxide dismutase, catalase, glutathione reductase and total glutathione content) in those cells. This was also consistent with the decreased in IC50 values observed after the incubation of these cells with C20/A80-DOX and C50/A50-DOX NPs (1.90-3.48 μg/mL) compared with free DOX (2.36-6.025 μg/mL). In vivo results suggested that the selected proportions of chitosan-BSA created nonhemolytic and biocompatible stable NPs at the selected dose of 20 mg/kg. Despite the different formulations, this study demonstrated that these NPs could serve as safe drug carriers in further in vivo investigations.

Keywords: Antitumour drugs; Biocompatibility; Drug delivery systems; In vivo; Nanoparticles; Tumor cells.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Intravenous
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / toxicity
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods
  • Chitosan / chemistry
  • Cross-Linking Reagents / chemistry
  • Delayed-Action Preparations
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacology
  • Doxorubicin / toxicity
  • Drug Carriers / chemistry*
  • Drug Delivery Systems*
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Inhibitory Concentration 50
  • Nanoparticles*
  • Rats
  • Rats, Wistar
  • Serum Albumin, Bovine / chemistry

Substances

  • Antibiotics, Antineoplastic
  • Cross-Linking Reagents
  • Delayed-Action Preparations
  • Drug Carriers
  • Serum Albumin, Bovine
  • Doxorubicin
  • Chitosan