Design, Evaluation, and Statistical Optimization of Nintedanib Solid Lipid Nanoparticles

Abstract

Introduction: Nintedanib (NTD), a triple tyrosine kinase inhibitor targeting vascular endothelial growth factor
receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor, is widely used in cancer
therapy but is limited by poor aqueous solubility and variable bioavailability. Solid lipid nanoparticles (SLNs)
offer a promising approach to enhance drug stability, entrapment, and sustained release. This study aimed to
formulate and statistically optimize NTD-loaded SLNs (NTD-SLNs). Materials and Methods: NTD-SLNs were
prepared using glyceryl monostearate as lipid, Tween 80 as surfactant, and Pluronic F-68 as stabilizer by the
solvent injection method. Response surface methodology was employed to optimize three formulation variables:
surfactant concentration, stabilizer concentration, and aqueous-to-organic phase ratio. The optimized formulation
was characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), drug
loading (DL), morphology scanning electron microscopy (SEM), and in vitro drug release using the dialysis
membrane technique. Results: The optimized SLNs exhibited a particle size of 246.2 nm and a PDI of 0.272,
closely matching predicted values, confirming model reliability. The formulation showed high EE (86.5 ± 3.33%),
DL (18.5 ± 1.2%), and percentage yield (94.3%). SEM images confirmed spherical and uniform nanoparticles.
In vitro release studies demonstrated sustained drug release, with 98.9% cumulative release over 24 h compared
to rapid release of pure NTD within 4 h. Conclusion: The optimized NTD-SLNs demonstrated favorable
physicochemical properties and sustained release behavior, indicating their potential to enhance therapeutic
performance and controlled delivery of NTD