Nanoformulations for Treating HIV-Associated Neurocognitive Disorders – IP 1656

With proper medications humanimmunodeficiency virus (HIV) patients now live almost full lifespans; however, HANDcontinues and its prevalence is increasing. This may be, in part, because HIVinfection remains in the brain. Anti-retroviral therapies (ARV)have been shown to improve cognition and reduce the prevalence ofHIV-associated dementia; however, continued HIV infection and aging processexacerbate the incidence of HAND. Since the beginning of the epidemic, drugabuse and HIV infection have been inextricably linked, and neurocognitivedysfunction is enhanced in HIV patients that are ingesting cocaine and otherdrugs of abuse. Cocaine causes neuronal impairments as well as increases the incidenceand severity of HAND. Despite significant therapeutic advances made in the managementof HIV, effective treatments against HIV infection in the brain and the pathogenesisof HAND remains a tremendous task. FIU inventors have developed compositionsand methods based on bifunctional plant molecule, Withaferine-A (WA), which caneradicate HIV and remove neuronal amyloid beta (Aβ) protein. The formulationscomprise magnetic nanoparticles (MENPs) encapsulated with liposomes, and conjugatedto or mixed with therapeutic cargos comprising an HIV inhibitor (WA), aninhibitor of beta-secretase 1 (BACE-1) activity or expression, and a cocaineantagonist. Because of the high magnetic moments of the MENPs, the formulationscan deliver therapeutic cargos to desired body areas including across the bloodbrain barrier (BBB) via the application of noninvasive external magnetic forces.The components of the therapeutic cargos are then sequentially released fromliposomes via biodegradation or diffusion, and alternating current (a.c.)trigger stimulation. Anne Laure Schmitt Olivier aschmitt@fiu.edu 305-348-5948