Glibenclamide-Loaded Nanoparticles Reduce NLRP3 Inflammasome Activation and Modulate miR-223-3p/miR-7-1-5p Expression...

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Glibenclamide (Glb), an anti-hyperglycemic drug, exhibits anti-inflammatory properties and can downregulate NLRP3 inflammasome activation, suggesting potential for neurodegenerative diseases.
• Poor solubility and bioavailability of Glb limit its therapeutic application. Bi-functionalized liposomes designed to cross the blood-brain barrier (BBB) offer a potential delivery system for CNS drug release.

Purpose of the Study:

• To investigate the in vitro effect of glibenclamide-loaded nanovectors (GNVs) and glibenclamide (Glb) on NLRP3 inflammasome activation in a cellular model.
• To evaluate the impact of GNVs and Glb on apoptosis-associated speck-like protein containing a CARD (ASC) aggregation, NLRP3 inflammasome-related cytokine production, and microRNA expression.

Main Methods:

• Utilized a lipopolysaccharide- and nigericin-activated THP-1 cell model to assess NLRP3 inflammasome activation.
• Quantified ASC speck oligomerization, NLRP3 gene and protein expression, and secretion of caspase 1, IL-1β, and IL-18.
• Measured concentrations of miR-223-3p and miR-7-1-5p, known modulators of the NLRP3 inflammasome.

Main Results:

• Both GNVs and Glb significantly reduced ASC speck oligomerization, NLRP3 transcription and translation, and secretion of caspase 1 and IL-1β.
• GNVs and Glb significantly suppressed miR-223-3p expression and upregulated miR-7-1-5p expression.
• These findings suggest GNVs effectively dampen NLRP3 inflammasome activation and inflammatory cytokine release, similar to Glb.

Conclusions:

• GNVs demonstrate potential as a novel strategy to reduce inflammasome activation in the central nervous system (CNS).
• The study highlights the ability of GNVs to mitigate neuroinflammation and modulate specific microRNAs, opening avenues for therapeutic applications in disease and rehabilitation.
• Further investigation is required to elucidate the complex mechanisms underlying the observed interactions between GNVs, Glb, and microRNA modulation.