title: Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model.
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.
authors.affiliation: Department of Experimental Medicine, University of Milano-Bicocca, Monza, Italy. francesca.re1@unimib.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Re
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cambianica
authors.forename: Cristiano
authors.initials: C
authors.lastname: Zona
authors.forename: Silvia
authors.initials: S
authors.lastname: Sesana
authors.forename: Maria
authors.initials: M
authors.lastname: Gregori
authors.forename: Roberta
authors.initials: R
authors.lastname: Rigolio
authors.forename: Barbara
authors.initials: B
authors.lastname: La Ferla
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicotra
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cagnotto
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.forename: Massimo
authors.initials: M
authors.lastname: Masserini
authors.forename: Giulio
authors.initials: G
authors.lastname: Sancini
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000737:chemistry*; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D003474:Curcumin / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008081:Liposomes; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000008:administration & dosage*; D010539:Permeability; D051381:Rats
chemical_list: D001057:Apolipoproteins E; D008081:Liposomes; D003474:Curcumin