title: Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier in mice.
abstract: Eradication of virus by sanctuary sites is a main goal in HIV management. The central nervous system (CNS) is a classic model of sanctuary where viral replication occurs despite a complete viral suppression in peripheral blood. In recent years, nanotechnologies have provided a great promise in the eradication of HIV from the CNS. We hereby demonstrate for the first time that the structurally complex antiretroviral drug enfuvirtide (Enf), which normally is unable to penetrate the cerebrospinal fluid, is allowed to cross the blood brain barrier (BBB) in mice by conjugation with a nanoconstruct. Iron oxide nanoparticles coated with an amphiphilic polymer increase Enf translocation across the BBB in both in vitro and in vivo models. The mechanism involves the uptake of nanoconjugated-Enf in the endothelial cells, the nanocomplex dissociation and the release of the peptide, which is eventually excreted by the cells in the brain parenchyma.
  
  
  BACKGROUND
  Despite the success of cocktail therapy of antiretroviral drugs, the complete eradication of HIV remains elusive, due to existence of viral sanctuary sites. The authors showed in this study that an antiretroviral drug complexed with iron oxide nanoparticles and coated with PMA amphiphilic polymer crosses the blood brain barrier. Furthermore, there was significant anti-viral activity. The results would aid further drug designs to eradicate HIV.
authors.affiliation: Ospedale L. Sacco, Milano, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Fiandra
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Ospedale L. Sacco, Milano, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Mazzucchelli
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università di Milano, Milano, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Truffi
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Santini
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università di Milano, Milano, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Allevi
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università di Milano, Milano, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.affiliation: Ospedale L. Sacco, Milano, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Capetti
authors.affiliation: Ospedale L. Sacco, Milano, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy; Laboratorio di Biofisica e Nanomedicina, Polo Tecnologico, Fondazione Don Gnocchi IRCCS-ONLUS, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Prosperi
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università di Milano, Milano, Italy. Electronic address: fabio.corsi@unimi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Corsi
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier; D002626:Chemistry, Pharmaceutical; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology
chemical_list: D019380:Anti-HIV Agents
keywords: Blood brain barrier; Enfuvirtide; HIV sanctuaries; PMA-coated nanoparticles