Fluorescent PLGA-FKR648 used to track nanoparticles ability to cross the blood-brain-barrier as part of development of HIV treatment

Human immunovirus (HIV) is a wide-spread and incurably lethal disease. The Blood-Brain-Barrier (BBB) separates the brain tissue from the bloodstream and is intended to keep the brain safe from potentially toxic molecules within the bloodstream. One of the more insidious aspects of HIV is the capacity of the virus to ‘hide’ within the brain tissue where most anti-viral medications cannot reach it due to the BBB. This makes treating HIV particularly difficult as the virus can re-infest a patient from surviving copies in the brain tissue, even if the majority of the viral replicates have been destroyed. Recently, researchers at Universidade do Porto (Portugal) and University of Helsinki (Finland) used fluorescent PLGA-FKR648 (PolyVivo AV015) from PolySciTech (www.polyscitech.com) as part of development of BBB crossing nanoparticles to attack HIV virus which hides in the brain. This fluorescently-tagged PLGA was used to develop nanoparticles which could be tracked by microscopy to observe their uptake across the barrier. By visualizing these particles, the researchers were able to validate the success of their particles in crossing the BBB. This research holds promise for improved therapeutic options for HIV.  Read more: Martins, Cláudia, Francisca Araújo, Maria João Gomes, Carlos Fernandes, Rute Nunes, Wei Li, Hélder A. Santos, Fernanda Borges, and Bruno Sarmento. "Using microfluidic platforms to develop CNS-targeted polymeric nanoparticles for HIV therapy." European Journal of Pharmaceutics and Biopharmaceutics (2018). https://www.sciencedirect.com/science/article/pii/S0939641117314820

“Abstract: The human immunodeficiency virus (HIV) uses the brain as reservoir, which turns it as a promising target to fight this pathology. Nanoparticles (NPs) of poly(lactic-co-glycolic) acid (PLGA) are potential carriers of anti-HIV drugs to the brain, since most of these antiretrovirals, as efavirenz (EFV), cannot surpass the blood–brain barrier (BBB). Forasmuch as the conventional production methods lack precise control over the final properties of particles, microfluidics emerged as a prospective alternative. This study aimed at developing EFV-loaded PLGA NPs through a conventional and microfluidic method, targeted to the BBB, in order to treat HIV neuropathology. Compared to the conventional method, NPs produced through microfluidics presented reduced size (73 nm versus 133 nm), comparable polydispersity (around 0.090), less negative zeta-potential (−14.1 mV versus −28.0 mV), higher EFV association efficiency (80.7% versus 32.7%) and higher drug loading (10.8% versus 3.2%). The microfluidics-produced NPs also demonstrated a sustained in vitro EFV release (50% released within the first 24 h). NPs functionalization with a transferrin receptor-binding peptide, envisaging BBB targeting, proved to be effective concerning nuclear magnetic resonance analysis (δ = −0.008 ppm; δ = −0.017 ppm). NPs demonstrated to be safe to BBB endothelial and neuron cells (metabolic activity above 70%), as well as non-hemolytic (1–2% of hemolysis, no morphological alterations on erythrocytes). Finally, functionalized nanosystems were able to interact more efficiently with BBB cells, and permeability of EFV associated with NPs through a BBB in vitro model was around 1.3-fold higher than the free drug. Keywords: Nanoparticles; Human immunodeficiency virus; Microfluidic production; Targeting; Blood-brain barrier”