Abstract
With proper medications human
immunodeficiency virus (HIV) patients now live almost full lifespans; however, HAND
continues and its prevalence is increasing. This may be, in part, because HIV
infection remains in the brain. Anti-retroviral therapies (ARV)
have been shown to improve cognition and reduce the prevalence of
HIV-associated dementia; however, continued HIV infection and aging process
exacerbate the incidence of HAND. Since the beginning of the epidemic, drug
abuse and HIV infection have been inextricably linked, and neurocognitive
dysfunction is enhanced in HIV patients that are ingesting cocaine and other
drugs of abuse. Cocaine causes neuronal impairments as well as increases the incidence
and severity of HAND. Despite significant therapeutic advances made in the management
of HIV, effective treatments against HIV infection in the brain and the pathogenesis
of HAND remains a tremendous task.FIU inventors have developed compositions
and methods based on bifunctional plant molecule, Withaferine-A (WA), which can
eradicate HIV and remove neuronal amyloid beta (Aβ) protein. The formulations
comprise magnetic nanoparticles (MENPs) encapsulated with liposomes, and conjugated
to or mixed with therapeutic cargos comprising an HIV inhibitor (WA), an
inhibitor of beta-secretase 1 (BACE-1) activity or expression, and a cocaine
antagonist. Because of the high magnetic moments of the MENPs, the formulations
can deliver therapeutic cargos to desired body areas including across the blood
brain barrier (BBB) via the application of noninvasive external magnetic forces.
The components of the therapeutic cargos are then sequentially released from
liposomes via biodegradation or diffusion, and alternating current (a.c.)
trigger stimulation.Benefit
Allows for non-invasive delivery of therapeutic cargo to desired body areas including across the blood brain barrier Permits the sequential release of several therapeutic components from one single biocompatible nanoformulationMarket Application
Treatment or prevention of amyloid plaque mediated neuronal dysfunction in HIV infected patientsPublications
Tiwari S, Atluri VSR, Yndart Arias A, et al. Withaferin A
Suppresses Beta Amyloid in APP Expressing Cells: Studies for Tat and Cocaine
Associated Neurological Dysfunctions. Front Aging Neurosci. 2018;10:291.
Published 2018 Sep 27. doi:10.3389/fnagi.2018.00291
