Loading of polymyxin B onto anionic mesoporous silica nanoparticles retains antibacterial activity and enhances biocompatibility

Int J Pharm. 2018 Feb 15;537(1-2):148-161. doi: 10.1016/j.ijpharm.2017.12.039. Epub 2017 Dec 24.

Abstract

Polymyxin B is a polycationic antibiotic used as the last line treatment against antibiotic-resistant Gram negative bacteria. However, application of polymyxin B is limited because of its toxicity effects. Herein, we used bare and surface modified mesoporous silica nanoparticles (MSNs) with an average diameter of 72.29 ± 8.17 nm as adsorbent for polymyxin B to improve its therapeutic properties. The polymyxin B adsorption onto MSN surfaces was explained as a function of pH, type of buffer and surface charge of nanoparticles, according to the ζ-potential of silica nanoparticles and adsorption kinetics results. The highest value of the adsorption capacity (about 401 ± 15.38 mg polymyxin B/ g silica nanoparticles) was obtained for the bare nanoparticles in Tris buffer, pH 9. Release profiles of polymyxin B showed a sustained release pattern, fitting Power law and Hill models. The antibiotic molecules-loaded nanoparticles showed enhanced antibacterial activity compared to free antibiotic against different Gram negative bacteria. Biocompatibility evaluation results revealed that loading of polymyxin B onto MSNs can decrease the cytotoxicity effects of the drug by reducing ROS generation. Our results suggest that formulation of drugs by adsorption onto MSNs may offer a way forward to overcome the adverse effects of some antibiotics such as polymyxin B without compromising their antimicrobial properties.

Keywords: Adsorption; Antibiotic; Drug delivery; Mesoporous silica nanoparticles; Polymyxin B.

MeSH terms

  • Adsorption / drug effects
  • Anions / chemistry*
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry*
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / chemistry*
  • Cell Line
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods
  • Drug Carriers / chemistry
  • Gram-Negative Bacteria / drug effects
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Nanoparticles / chemistry*
  • Particle Size
  • Polymyxin B / chemistry*
  • Porosity / drug effects
  • Reactive Oxygen Species / metabolism
  • Silicon Dioxide / chemistry*

Substances

  • Anions
  • Anti-Bacterial Agents
  • Biocompatible Materials
  • Drug Carriers
  • Reactive Oxygen Species
  • Silicon Dioxide
  • Polymyxin B