PLGA-Encapsulated Elvitegravir and Curcumin Modulates ART Penetration, Oxidative Stress, and Inflammation

Area of Science:

• Neuroscience
• Nanotechnology
• Pharmacology

Background:

• HIV establishes persistent reservoirs in the CNS, driving neuroinflammation and neuronal damage contributing to HAND.
• Current antiretroviral therapy (ART) faces challenges in effectively reaching CNS reservoirs.
• Nanoparticle drug delivery systems, specifically poly(lactic-co-glycolic acid) (PLGA) nanoparticles, show potential for improved ART delivery to the brain.

Purpose of the Study:

• To evaluate the efficacy of co-administered PLGA nanoparticles encapsulating elvitegravir (EVG) and curcumin (CUR).
• To assess the potential of this strategy in targeting CNS HIV reservoirs, reducing neuroinflammation, and mitigating oxidative stress.

Main Methods:

• PLGA nanoparticles encapsulating EVG and CUR were prepared using nanoprecipitation.
• Nanoparticle characterization included size, zeta potential, and encapsulation efficiency.
• In vitro studies used U1 macrophages, and in vivo studies utilized Balb/c mice to analyze cytokine levels, oxidative stress markers, and neuronal markers.

Main Results:

• PLGA-EVG and PLGA-CUR nanoparticles exhibited high encapsulation efficiency and sizes conducive to blood-brain barrier (BBB) permeability.
• In vitro, nanoparticles enhanced intracellular EVG, reduced pro-inflammatory cytokines, and improved antioxidant capacity.
• In vivo, co-administration improved CNS drug delivery, decreased neuroinflammation and oxidative stress, and preserved neuronal markers.

Conclusions:

• PLGA-based co-delivery of EVG and CUR effectively enhances ART delivery to the CNS.
• This nanoparticle strategy mitigates neuroinflammation and oxidative stress, showing potential for improved HAND therapies.
• Further research is needed to optimize formulations and assess long-term safety in chronic HIV settings.