Engineering Teriflunomide Solid Lipid Nanoparticles via Response Surface Methodology: Formulation Optimization and In Vitro Performance Evaluation
DOI:
https://doi.org/10.22159/ijap.2026v18i5.58690Keywords:
Teriflunomide, MS, SLNs, Box–behnken, miRNA complexation, and cellular uptakeAbstract
Objective: Multiple sclerosis is a chronic inflammatory disorder of the central nervous system, commonly managed with Teriflunomide, a poorly water-soluble BCS Class II drug. The present study was designed to develop and optimize Teriflunomide-loaded solid lipid nanoparticles (TFE-SLNs) to improve its solubility and drug release profile.
Methods: TFE-SLNs were prepared using the high-pressure homogenization technique with Compritol 888 ATO as the lipid and Tween 80 as the surfactant. A Box–Behnken design was employed to optimize critical formulation variables, including lipid concentration, surfactant concentration, and homogenization speed. The formulations were evaluated for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). The optimized SLNs were further characterized using FTIR, DSC, XRD, and SEM analyses, along with in vitro drug release, stability studies, miRNA complexation, and cellular uptake investigations.
Results: The optimized SLNs exhibited a particle size of 264.16 nm, PDI of 0.339, zeta potential of 28.8 mV, and entrapment efficiency of 69.12%. ANOVA confirmed the statistical significance of the model (p < 0.0001; R² > 0.98). The formulation demonstrated a sustained release profile (98.3% at 72 h) compared to the pure drug (29.3%), following the Korsmeyer–Peppas kinetic model. Characterization studies indicated good compatibility, reduced crystallinity, satisfactory stability, and enhanced cellular uptake.
Conclusion: Optimized TFE-SLNs demonstrated enhanced solubility, improved encapsulation efficiency, and sustained drug release, indicating their potential as an effective delivery system for Teriflunomide in the management of multiple sclerosis.
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