Quantitation of nanoparticle accumulation in flow using optimized microfluidic chambers

J. Kusunose, M. K J Gagnon, Jai Seo, K. W. Ferrara

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: The vascular cell adhesion molecule-1 (VCAM-1) targeting peptide sequence, VHPKQHR, is a promising moiety for targeting atherosclerosis through incorporation into nanoparticles such as dendrimers and liposomes. Purpose: We aim to develop VCAM-1-targeted nanoparticles that effectively accumulate on the endothelium under shear conditions and to develop robust microfluidic chambers able to house sufficient cells for flow cytometric measurements. Methods: Carboxyfluorescein-labeled monomeric VHP-peptide, tetrameric VHP-dendrimers (bisbidentate or radial architecture, with or without N-terminal acetylation) and VHP-peptide liposomes were prepared. Human umbilical vein endothelial cells were treated with nanoparticles under 0 or 2.9 dyne/cm2 shear, and particle binding was quantified. Flow chambers cured at various temperatures, with or without glass backings were fabricated, characterized for deformation and applied in experiments. Results: Although liposomes accumulated with highest efficiency, dendrimers also demonstrated specific binding. N-terminal acetylation significantly reduced dendrimer binding, and despite shorter movement range, bisbidentate dendrimers outperformed radial dendrimers, suggesting multiple epitope presence within its estimated arm-span of 57Å. Under shear, while liposome binding increased 300%, dendrimer binding to cells decreased 65%. Through higher temperature curing and glass backing insertion, polydimethylsiloxane flow chambers maintaining rectangular cross-section with aspect-ratio as low as 1:111 were achieved. Conclusion: Optimized dendrimers and liposomal nanocarriers specifically accumulated onto cells within microfluidic chambers.

Original languageEnglish (US)
Pages (from-to)48-56
Number of pages9
JournalJournal of Drug Targeting
Volume22
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • Atherosclerosis
  • Dendrimers
  • in vitro model
  • Liposomes
  • Peptide
  • Targeted drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Quantitation of nanoparticle accumulation in flow using optimized microfluidic chambers'. Together they form a unique fingerprint.

  • Cite this