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

Maria Gregori, Daniela Bertani, Emanuela Cazzaniga, Antonina Orlando, Michele Mauri, Alberto Bianchi, Francesca Re, Silvia Sesana, Stefania Minniti, Maura Francolini, Alfredo Cagnotto, Mario Salmona, Luca Nardo, Domenico Salerno, Francesco Mantegazza, Massimo Masserini, Roberto Simonutti

Research output: Contribution to journalArticlepeer-review

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. In the search of novel drug carriers for brain drug delivery, poly(N,N-dimethylacrylamide)-b-polystyrene nanoparticles (NP) have been functionalized with a modified fragment of Apolipoprotein E (mApoE). These NP show to be uptaken and to overcome a Blood-Brain Barrier (BBB) in vitro cellular model. The cytotoxicity of NP is also investigated on different cell lines, showing high biocompatibility.

Original languageEnglish
Pages (from-to)1687-1697
Number of pages11
JournalMacromolecular Bioscience
Volume15
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

Keywords

  • blood-brain barrier
  • controlled drug release
  • copolymers
  • drug delivery
  • nanoparticles

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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