Development and in-vivo characterization of Pyrazinamide-Loaded Solid Lipid and PLGA Nanoparticles

Abstract

Pyrazinamide is an important first-line antitubercular drug used in combination therapy for the treatment of tuberculosis. However, conventional oral dosage forms may lead to fluctuations in plasma drug levels and limited tissue retention. The present study aimed to develop and evaluate pyrazinamide-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles and solid lipid nanoparticles (SLNs) for improved drug delivery and tissue distribution. PLGA nanoparticles were prepared using a modified multiple emulsion solvent evaporation method, while SLNs were formulated using the hot high-shear homogenization technique employing glyceryl dibehenate as lipid matrix and Tween 80 as surfactant. Optimization of formulation variables was performed using response surface methodology through Box–Behnken design and Central Composite Design to study the effect of formulation parameters on particle size, encapsulation efficiency, and drug release profile. The optimized formulations were evaluated for in vivo drug distribution in Albino Wistar rats by determining drug levels in organs such as liver, spleen, and lungs. The results demonstrated that nanoparticle-based formulations provided improved drug distribution and sustained drug levels in tissues compared with free drug administration. No significant accumulation of drug was observed after repeated dosing, indicating safe and controlled delivery. The findings suggest that SLN and PLGA nanoparticles are promising nanocarrier systems for enhancing the therapeutic performance of pyrazinamide in tuberculosis treatment.

Keywords: Pyrazinamide; Solid Lipid Nanoparticles; PLGA Nanoparticles; Nanocarrier Drug Delivery; Tuberculosis Therapy; In Vivo Drug Distribution; Controlled Drug Release.