Formulation and Optimization of Pyrazinamide-Loaded Solid Lipid Nanoparticles by Employing a Design of Experiments...

Area of Science:

• Nanotechnology
• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Tuberculosis (TB) is a global health crisis requiring innovative therapies.
• Pyrazinamide (PYZ) is a crucial first-line anti-TB drug but causes dose-dependent hepatotoxicity.
• Developing safer and more effective PYZ delivery methods is essential.

Purpose of the Study:

• To formulate and optimize pyrazinamide-loaded solid lipid nanoparticles (PYZ-SLNs) for enhanced TB treatment.
• To evaluate the physicochemical properties and stability of PYZ-SLNs.
• To investigate the potential of PYZ-SLNs to circumvent hepatic first-pass metabolism.

Main Methods:

• PYZ-SLNs were prepared using high-pressure homogenization and optimized via a 2³-factorial design.
• Critical formulation parameters included drug concentration, emulsifier concentration, and homogenization cycles.
• Key quality attributes assessed were entrapment efficiency (EE%), drug loading (DL%), and particle size.

Main Results:

• Optimized PYZ-SLNs exhibited a particle size of 401±08 nm, 86.24±1.15% EE, and 14.38±0.85% DL.
• In vitro studies confirmed PYZ-SLN stability in gastrointestinal media and an anti-lipolytic effect.
• Drug release followed the Hixon-Crowell model, and accelerated stability studies showed no significant changes over 6 months.

Conclusions:

• PYZ-SLNs demonstrate excellent physicochemical properties and stability for oral administration.
• The formulation shows potential for targeting the intestinal lymphatic pathway, bypassing hepatic metabolism.
• PYZ-SLNs represent a promising strategy to mitigate PYZ-induced hepatotoxicity in TB treatment.