Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model

Francesca Re, Ilaria Cambianica, Cristiano Zona, Silvia Sesana, Maria Gregori, Roberta Rigolio, Barbara La Ferla, Francesco Nicotra, Gianluigi Forloni, Alfredo Cagnotto, Mario Salmona, Massimo Masserini, Giulio Sancini

Research output: Contribution to journalArticlepeer-review

Abstract

A promising strategy to enhance blood-brain barrier penetration by drugs is the functionalization of nanocarriers with uptake-facilitating ligands. We studied the cellular uptake, by cultured RBE4 brain capillary endothelial cells, of nanoliposomes (NLs) covalently coupled with monomer or tandem dimer of apolipoprotein E (ApoE)-derived peptides (residues 141-150), at various densities. NLs without functionalization did not show either relevant membrane accumulation or cellular uptake, as monitored by confocal microscopy and quantified by fluorescence-activated cell sorting. Functionalization with peptides mediated an efficient NLs uptake that increased with peptide density; NLs carrying monomeric peptide performed the best. Moreover, we studied the ability of ApoE-NLs to enhance the transport of a drug payload through a RBE4 cell monolayer. The permeability of a tritiated curcumin derivative was enhanced after its entrapment into ApoE-NLs, in particular those functionalized with the dimer (+83% with respect to free drug, P <0.01). Thus, these NLs appear particularly suitable for implementing further strategies for drug brain targeting. From the Clinical Editor: Re and her collaborators present a method for delivering nanoliposomes via the blood brain barrier by utilizing peptide fragments including monomers or tandem dimers ApoE. This method may enable enhanced nanoliposome associated drug delivery via the blood-brain barrier, which would have enormous significance in neurodegenerative and other CNS disorders.

Original languageEnglish
Pages (from-to)551-559
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume7
Issue number5
DOIs
Publication statusPublished - Oct 2011

Keywords

  • ApoE peptide
  • Blood-brain barrier
  • Brain endothelial cells
  • Nanoliposomes

ASJC Scopus subject areas

  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering
  • Materials Science(all)
  • Medicine (miscellaneous)
  • Pharmaceutical Science

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