New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy

Area of Science:

• Pharmacology
• Drug Delivery
• Neuroscience

Background:

• Chemotherapy-induced peripheral neuropathy (CIPN) presents a significant clinical challenge with limited treatment options.
• Existing PPARα agonists like fenofibrate have limitations including low affinity and poor bioavailability.
• A190, a selective PPARα agonist, shows promise but suffers from poor solubility and bioavailability.

Purpose of the Study:

• To develop and characterize an optimized oil-in-water (o/w) microemulsion formulation for A190.
• To enhance the solubility, intestinal permeability, and oral bioavailability of A190.
• To evaluate the efficacy of A190 microemulsion in preclinical models of neuropathic and inflammatory pain.

Main Methods:

• Utilized Box-Behnken design for microemulsion optimization.
• Assessed physical stability, droplet size, and drug loading efficiency.
• Measured effective and apparent permeability, cell viability, and oral bioavailability in vivo.
• Evaluated A190 microemulsion efficacy in CIPN and complete Freund's adjuvant-induced pain models.

Main Results:

• Developed a stable A190 microemulsion with ~100 nm droplet size and >95% drug loading.
• Demonstrated significantly enhanced permeability and ~5-fold increased oral bioavailability compared to A190 dispersion.
• Confirmed good biocompatibility with no significant impact on cell viability.
• Showed effective reduction of mechanical hypersensitivity in CIPN and reduced pain in inflammatory models.

Conclusions:

• The developed A190 microemulsion effectively overcomes the solubility and bioavailability limitations of A190.
• A190 microemulsion demonstrates significant therapeutic potential for managing CIPN and chronic inflammatory pain.
• This formulation highlights a promising non-opioid strategy for neuropathic pain treatment.