Investigation of Functionalized Poly(N,N-dimethylacrylamide)-block-polystyrene Nanoparticles As Novel Drug Delivery System to Overcome the Blood-Brain Barrier In Vitro

Macromol Biosci. 2015 Dec;15(12):1687-97. doi: 10.1002/mabi.201500172. Epub 2015 Jul 21.

Abstract

In the search of new drug delivery carriers for the brain, self-assembled nanoparticles (NP) were prepared from poly(N,N-dimethylacrylamide)-block-polystyrene polymer. NP displayed biocompatibility on cultured endothelial cells, macrophages and differentiated SH-SY5Y neuronal-like cells. The surface-functionalization of NP with a modified fragment of human Apolipoprotein E (mApoE) enhanced the uptake of NP by cultured human brain capillary endothelial cells, as assessed by confocal microscopy, and their permeability through a Transwell Blood Brain Barrier model made with the same cells, as assessed by fluorescence. Finally, mApoE-NP embedding doxorubicin displayed an enhanced release of drug at low pH, suggesting the potential use of these NP for the treatment of brain tumors.

Keywords: blood-brain barrier; controlled drug release; copolymers; drug delivery; nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / chemistry*
  • Apolipoproteins E* / chemistry
  • Apolipoproteins E* / pharmacokinetics
  • Apolipoproteins E* / pharmacology
  • Blood-Brain Barrier / metabolism*
  • Cell Line
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Drug Carriers* / pharmacology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Nanoparticles / chemistry*
  • Polystyrenes / chemistry*

Substances

  • Acrylamides
  • Apolipoproteins E
  • Drug Carriers
  • Polystyrenes
  • poly(N,N-dimethylacrylamide)
  • Doxorubicin