Low nanogel stiffness favors nanogel transcytosis across an in vitro blood-brain barrier

Laís Ribovski, Edwin de Jong, Olga Mergel, Guangyue Zu, Damla Keskin, Patrick van Rijn, Inge S Zuhorn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Transport of therapeutics across the blood-brain barrier (BBB) is a fundamental requirement for effective treatment of numerous brain diseases. However, most therapeutics (>500 Da) are unable to permeate through the BBB and do not achieve therapeutic doses. Nanoparticles (NPs) are being investigated to facilitate drug delivery to the brain. Here, we investigate the effect of nanoparticle stiffness on NP transport across an in vitro BBB model. To this end, fluorescently labeled poly(N-isopropylmethacrylamide) (p(NIPMAM)) nanogels' stiffness was varied by the inclusion of 1.5 mol% (NG1.5), 5 mol% (NG5), and 14 mol% (NG14) N,N'-methylenebis(acrylamide) (BIS) cross-linker and nanogel uptake and transcytosis was quantified. The more densely cross-linked p(NIPMAM) nanogels showed the highest level of uptake by polarized brain endothelial cells, whereas the less densely cross-linked nanogels demonstrated the highest transcytotic potential. These findings suggest that nanogel stiffness has opposing effects on nanogel uptake and transcytosis at the BBB. (C) 2021 The Authors. Published by Elsevier Inc.

Original languageEnglish
Article number102377
Number of pages11
JournalNanomedicine-Nanotechnology biology and medicine
Volume34
Early online date20-Feb-2021
DOIs
Publication statusPublished - Jun-2021

Keywords

  • Nanoparticles
  • Blood-brain barrier
  • Nanogel
  • Stiffness
  • Transcytosis
  • SOLID LIPID NANOPARTICLES
  • ENDOTHELIAL-CELLS
  • CELLULAR UPTAKE
  • PROTEIN CORONA
  • DRUG-DELIVERY
  • TRANSPORT
  • BIOCOMPATIBILITY
  • TRANSFERRIN
  • CIRCULATION
  • ENDOCYTOSIS

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