Ionic Liquid Coating-Driven Nanoparticle Delivery to the Brain: Applications for NeuroHIV

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Neuroscience

Background:

• Central nervous system (CNS) drug delivery is challenging, limiting treatment of infections like HIV.
• HIV establishes a latent reservoir in the CNS, causing neurological deficits (neuroHIV) resistant to systemic antiretrovirals (ARTs).

Purpose of the Study:

• To develop novel bioinspired ionic liquid-coated nanoparticles (IL-NPs) for enhanced CNS drug delivery.
• To investigate the efficacy of IL-NPs in delivering ARTs to the brain and targeting specific CNS cells.

Main Methods:

• Development of IL-NPs using ionic liquid choline trans-2-hexenoate (CA2HA 1:2) for coating.
• Intracarotid arterial infusion in a model system to assess brain delivery and cellular accumulation.
• Loading of abacavir (ABC), an ART, into IL-NPs and in vitro efficacy testing.
• Cytotoxicity assays on human peripheral blood mononuclear cells (PBMCs) and neural cells.

Main Results:

• IL-NPs achieved 48% brain delivery of intracarotid infused cargo.
• CA2HA 1:2 coating showed preferential accumulation in parenchymal microglia over endothelial cells.
• Successfully loaded abacavir (ABC) retained antiviral efficacy in vitro.
• IL-NPs and CA2HA 1:2 coating demonstrated no cytotoxicity and possessed anti-viremic capacity.
• Enhanced uptake of IL-NPs into neural cells compared to bare nanoparticles.

Conclusions:

• Bioinspired IL-NPs represent a promising strategy for overcoming the blood-brain barrier for CNS drug delivery.
• This technology has the potential to revolutionize the treatment of neuroHIV and other CNS disorders.
• IL-NPs can be engineered to target specific neural cells, improving therapeutic outcomes.