Combination therapy using brain accumulating polymeric nanoparticles for tackling HIV-infected brain reservoirs in drug abuse population

N. Kolishetti, B. Surnar, A.S. Shah, R. Ramirez-Jaime, V. Atluri, A.Y. Arias, M. Nair, S. Dhar
Florida International University,
United States

Keywords: nanomedicine, Drug abuse, Reactive oxygen species, aspirin


Human immunodeficiency virus (HIV) infection in the brain and HIV-associated neurocognitive disorders (HAND) are major issues to patients with HIV. Most of the therapeutic options cannot be used to tackle the virus in the brain and treat HAND, due to the inability of antiretroviral drugs and neuroprotectants to cross the blood-brain barrier (BBB). Nano-formulations have shown significant promise in medicine for therapy and diagnosis of various diseases. Recently polymeric nano-formulations made using FDA approved poly(lactic-co-glycolic) acid (PLGA), and polyethylene glycol (PEG) functionalized with a terminal triphenylphosphonium (TPP) cation were shown to accumulate in brain using various animal models. In this work, we examined a combined antiretroviral therapy along with antioxidant- and anti-inflammatory-based neuroprotectants using biodegradable PLGA-PEG-TPP, based polymeric nanoparticle to reduce the burden caused by viral reservoirs in the brain and tackle the oxidative stress and inflammation in astrocytes and microglia. A major achievement in this work is to optimize and deliver antiretroviral drug-loaded nanoparticles which can reduce the viral reservoirs. Data from selective antiviral loaded nanoparticles in reducing the viral load will be discussed. HIV-induced neurodegeneration further become worse in the presence of recreational drugs. We will discuss our data on therapeutic and protective effects of our antiviral and neuroprotectant-loaded nanoparticles.