Impact of polyethylene glycol polymers on the physicochemical properties and mucoadhesivity of itraconazole nanoparticles

Eur J Pharm Biopharm. 2019 Nov;144:57-67. doi: 10.1016/j.ejpb.2019.09.004. Epub 2019 Sep 4.

Abstract

Itraconazole (ITR) is a broad-spectrum antifungal drug with a very low solubility. In this work, the application of a heat induced evaporative antisolvent nanoprecipitation process yielded disordered nanoparticles (NPs) of ITR. The inclusion of different types of poly(ethylene glycol) (PEG) allowed PEGylation of NPs by adsorption to be achieved. The NP dispersions were composed of monodispersed particles in a nanometric size range (<290 nm) and although PEGylation had no impact on the average particle size, the surface potential was partially neutralised in the modified NPs. The solid state analysis using powder X-ray diffraction and thermal analysis revealed a disordered, liquid crystalline smectic organisation of the non-PEGylated NPs, while some of the PEGylated NPs were more crystalline. The PEGylated NPs exhibited mucoadhesive potential in stationary conditions (dynamic light scattering analysis) but when flow conditions were applied (nanoparticle tracking analysis and quartz crystal microbalance with dissipation) the particles had mucopenetrative properties. The non-PEGylated ITR NPs did not interact with mucin and therefore, this system was considered as having a mucopenetrative character. This study demonstrates that the properties of NPs made of organic drug molecules can be modified by the addition of polymers, which may impact on their interaction with mucin and therefore on their potential systemic absorption.

Keywords: Itraconazole; Liquid crystal; Mucoadhesivity; Nanoparticle tracking analysis; Nanoparticles; PEGylation; Poly(ethylene glycol); Quartz crystal microbalance with dissipation; Thermal analysis.

MeSH terms

  • Adhesives / chemistry*
  • Adsorption / drug effects
  • Antifungal Agents / chemistry
  • Drug Carriers / chemistry
  • Drug Compounding / methods
  • Itraconazole / chemistry*
  • Nanoparticles / chemistry*
  • Particle Size
  • Polyethylene Glycols / chemistry*
  • Polymers / chemistry*
  • Solubility / drug effects
  • Surface Properties / drug effects

Substances

  • Adhesives
  • Antifungal Agents
  • Drug Carriers
  • Polymers
  • Itraconazole
  • Polyethylene Glycols