Potential role of nanopharmacology in reducing neuroinflammation associated with hypertension and metabolic disorders

Abstract

Hypertension disrupts cerebral blood flow, leading to endothelial dysfunction, breakdown of the blood-brain barrier (BBB), and inflammatory cell infiltration. This cascade triggers glial cell activation, increases oxidative stress, and causes pro-inflammatory cytokine release, creating a neurotoxic environment. In this context, we explore the intricate connection between hypertension, neuroinflammation, and neurodegeneration, as well as how hypertension interacts with other metabolic disorders, such as obesity and diabetes, to further worsen neuroinflammation. Additionally, we discuss the role of the renin-angiotensin-aldosterone system, the impact of the microbiome, and the potential contribution of chronic infections in exacerbating neuroinflammation. It is essential to emphasize the potential of nanotechnology to transform therapeutic approaches. Nanoparticle-based drug delivery systems can enhance the bioavailability and selectivity of antihypertensive drugs, antioxidants, and neuroprotective compounds, enabling targeted delivery across the BBB. By combining effective blood pressure management with nanotechnology-enabled therapies that modulate inflammation, oxidative stress, and protein aggregation, we can explore new avenues for preventing and treating hypertension and metabolic disorder-associated neurodegenerative conditions. Ultimately, hypertension significantly contributes to neuroinflammation and neurodegeneration by promoting neuronal cell death, primarily through impaired cerebral blood flow and disruption of the BBB. The interaction of hypertension with metabolic disorders exacerbates these effects. However, advancements in our understanding and new technologies reveal promising nanopharmacological approaches for targeted drug delivery to the brain, thereby improving treatment outcomes, enhancing adherence, and reducing side effects.

Keywords: Neuroinflammation; Nanotechnology/nanopharmacology; Blood-brain barrier; Oxidative stress; Neurodegeneration; Hypertension; Metabolic disorders

Core Tip: This mini-review unveils the intricate nexus between hypertension, metabolic disorders, and neurodegeneration, spotlighting neuroinflammation as a pivotal mediator. Compromised cerebral blood flow and blood-brain barrier (BBB) disruption initiate a cascade of oxidative stress and pro-inflammatory cytokine release, culminating in neuronal injury. We advocate for the transformative potential of nanopharmacology. Nanoparticle-mediated drug delivery offers a strategic avenue to enhance therapeutic bioavailability and selectivity, enabling targeted intervention across the BBB. By synergizing effective blood pressure management with nanotechnology-driven modulation of neuroinflammation, we pioneer novel strategies to mitigate neurodegenerative pathologies. This paradigm shift holds promise for revolutionizing therapeutic approaches, paving the way for improved patient outcomes in hypertension-associated neurological disorders.