The brain is one of the final hiding places of HIV from combination antiretroviral therapy. Modern treatments effectively suppress levels of the virus in most parts of the body but struggle to cross the blood-brain barrier, allowing reservoirs to form in the central nervous system. The need to wipe out the reservoirs has spurred research into nanoparticles capable of entering the brain.
Researchers at the University of Miami shared details of their efforts to get antiretroviral therapy into the brain in a paper published in the journal ACS Nano. The paper describes the use of biodegradable brain-targeted polymeric nanoparticles to reduce the brain viral burden in an animal model of HIV.
The researchers used the nanoparticles to combine the antiretroviral therapy with antioxidant and anti-inflammatory neuroprotectants, creating a treatment with the potential to tackle both the viral reservoir and oxidative stress and inflammation. The approach could theoretically be used to hustle other therapeutic molecules across the blood-brain barrier.
Interest in applying the nanoparticle technology to HIV reflects the persistence of neurocognitive disorders despite improvements in the management of the infection. While dementia is now rare in people living with the virus, HIV-associated neurocognitive disorders that affect cognitive functions such as concentration and memory remain a problem.
Recreational drug use can increase the risk of neuroinflammation linked to HIV-associated neurocognitive disorders, leading the Miami researchers to study their nanoparticle formulation in a methamphetamine-exposed animal model. Including antioxidant and anti-inflammatory neuroprotectants gives the formulation the potential to tackle neuroinflammation.
The paper is part of a string of publications from groups seeking to get antiretroviral therapies into the brain. Last year, researchers at the University of Tennessee published a paper describing the use of a poloxamer-PLGA nanoformulation to deliver elvitegravir, the active ingredient in combination therapies and Gilead’s now-withdrawn Vitekta, to cells in the brain.