Enhanced Drug Delivery into Cell Cytosol via Glycoprotein H-Derived Peptide Conjugated Nanoemulsions

ACS Nano. 2017 Oct 24;11(10):9802-9813. doi: 10.1021/acsnano.7b03058. Epub 2017 Aug 28.

Abstract

The key role of nanocarriers in improving the pharmacological properties of commonly used drugs is recognized worldwide. It is also known that in the development of new effective nanocarriers the use of targeting moieties integrated on their surface is essential. Herein, we propose a nanocarrier based on an oil in water nanoemulsion coated with a membranotropic peptide derived from the glycoprotein H of Herpes simplex virus 1, known as gH625, in order to reduce endolysosomal accumulation and to enhance cytosolic localization. In addition, we show an enhanced anti-inflammatory activity of curcumin, a bioactive compound isolated from the Curcuma longa plant, when loaded into our engineered nanocarriers. This effect is a consequence of a higher uptake combined with a high curcumin preservation exerted by the active nanocapsules compared to control ones. When loaded into our nanocapsules, indeed, curcumin molecules are directly internalized into the cytosol rather than into lysosomes. Further, in order to extend the in vitro experimental setting with a more complex model and to explore the possibility to use our nanocarriers for further biological applications, we tested their performance in a 3D sprouting angiogenesis model. Finally, we show promising preliminary in vivo results by assessing the anti-inflammatory properties of the proposed nanocarrier.

Keywords: curcumin; drug delivery; gH625; nanocapsules; nanoemulsions.

MeSH terms

  • Curcumin / chemistry
  • Curcumin / pharmacokinetics*
  • Cytosol / chemistry
  • Cytosol / metabolism*
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Emulsions / chemistry
  • Emulsions / metabolism
  • Human Umbilical Vein Endothelial Cells / chemistry
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Peptides / chemistry
  • Peptides / metabolism*
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism*

Substances

  • Drug Carriers
  • Emulsions
  • Peptides
  • Viral Proteins
  • bovine herpesvirus type-1 glycoproteins
  • Curcumin