Novel drug delivery modality to suppress HIV neuropathogenesis 4085

Description Despite significant advances in HIV treatment, neuroHIV and HIV-associated neurocognitive disorder (HAND) remain persistent challenges. A major issue is that most antiretroviral regimens fail to achieve therapeutic concentrations in the brain, allowing HIV to continue within brain and cause neuroinflammation. Therefore, finding a novel drug delivery modality to treat neuroHIV and HAND is critically important. Our laboratory has been developing synthetic lipids and extracellular vesicle-based (EV-Lip) hybrid drug delivery system for antiretroviral drugs using intranasal route effectively and suppress HIV-associated neuropathogenesis. We have developed and characterized EV-Lip-based drug delivery system for the delivery of antiretroviral therapy (ART) drugs in brain. Our study has shown that an RT drugs when encapsulated in EV-Lip system using intranasal delivery can significantly increase the brain drug concentration and reduce off-target effects in liver, plasma, and lungs in wild-type mice. Our findings also showed that EV-Li-ART drug can suppress HIV-associated neuroinflammation, oxidative DNA damage, and neuronal damage. Finally, we have shown that the formulation significantly reduces HIV-associated motor and cognitive impairments in EcoHIV mice, and a nutraceutical adjuvant reduced HIV-associated neuroinflammation and cognitive impairments. We conclude that EV-Lip hybrid system using intranasal route could be a better alternative to treat HIV-associated neuropathology. Funding Sources NIH R21AG081140 Topic Categories Neuroimmunology (NEUR)