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Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier in mice

Significance Statement

HIV replication plays a major role in neurological diseases, and CNS is one of the main viral reservoirs. Unfortunately many drugs including anti-HIV therapeutic molecules don’t cross the blood brain barrier. The research team from University of Milano developed a novel nanodrug consisting of an iron oxide nanoparticle coated with an amphiphilic polymer and functionalized with the antiretroviral peptide enfuvirtide. The authors demonstrated the increase in enfuvirtide delivery as a nanoconjugate across the blood brain barrier in both in vitro and in vivo. This study opens the way for similar nanoparticle functionalized to be delivered to the brain.

Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier- global medical discovery

Journal Reference

Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier in mice

Nanomedicine. 2015 Aug;11(6):1387-97.

Fiandra L1, Colombo M2, Mazzucchelli S1, Truffi M3, Santini B2, Allevi R3, Nebuloni M3, Capetti A1, Rizzardini G1, Prosperi D4,Corsi F5.

Show Affiliations

1Ospedale L. Sacco, Milano, Italy.

2Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy.

3Dipartimento di Scienze Biomediche e Cliniche “Luigi Sacco”, Università di Milano, Milano, Italy.

4Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy; Laboratorio di Biofisica e Nanomedicina, Polo Tecnologico, Fondazione Don Gnocchi IRCCS-ONLUS, Milan, Italy.

5Dipartimento di Scienze Biomediche e Cliniche “Luigi Sacco”, Università di Milano, Milano, Italy. Electronic address: [email protected]

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.

FROM THE CLINICAL EDITOR:
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.

Copyright © 2015 Elsevier Inc. All rights reserved.

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