Formulation, Characterization, and Preliminary In Vitro Evaluation of Letrozole Incorporated Eudragit® RS 100 Nanoparticles Using HepG2 Cells.
TL;DR
The obtained results confirmed the successful development of LTZ-loaded polymeric nanoparticles with suitable physicochemical properties, efficient drug encapsulation, and sustained release behavior and preserved the cytotoxic activity of LTZ, indicating their potential as an effective drug delivery system.
Abstract
INTRODUCTION/
Objective
Letrozole (LTZ)-loaded polymeric nanoparticles (PNPs) were formulated with Eudragit® RS100 to investigate their potential as a preliminary drug delivery system for hepatocellular carcinoma (HCC).
Methods
Nanoparticles were prepared using the spray-drying technique with a Büchi B-90 Nano Spray Dryer and characterized in terms of morphology, particle size, polydispersity index (PDI), zeta potential, drug loading efficiency, thermal and structural characteristics, in vitro release behavior, and preliminary cytotoxicity.
Results
SEM analysis demonstrated the formation of predominantly spherical particles with relatively smooth surfaces. The prepared nanoparticles exhibited initial particle sizes ranging between 253 nm and 425 nm, with PDI values of 0.3-0.4 and positive zeta potential values between 36 and 48 mV. Encapsulation efficiency (EE%) and drug loading (DL%) values were determined as 47.9%-56.9% and 9.1%-18.6%, respectively. Thermal and structural analyses indicated the molecular dispersion of LTZ within the polymeric matrix. In vitro release studies conducted at pH 7.4 demonstrated an initial burst release, followed by a sustained drug release profile over 24 h, with cumulative drug release reaching almost 80%. The preliminary cytotoxicity of the formulations was evaluated using the methylthiazolyl-diphenyl-tetrazolium bromide (MTT) assay on human hepatocellular carcinoma (HepG2) and healthy human dermal fibroblast (BJ) cell lines. Free LTZ demonstrated an IC50 value of 142.76 µg/mL against HepG2 cells, whereas the optimized nanoparticle formulation exhibited an IC50 value higher than 121.85 µg/mL.
Discussion
The obtained results confirmed the successful development of LTZ-loaded polymeric nanoparticles with suitable physicochemical properties, efficient drug encapsulation, and sustained release behavior. The positive surface charge and nanoscale size may support formulation stability. Furthermore, the nanoparticles preserved the cytotoxic activity of LTZ, indicating their potential as an effective drug delivery system.
Conclusion
Overall, the findings suggest that the developed nanoparticles constitute a promising drug delivery system for further investigation in HCC-related therapy. However, additional mechanistic studies and in vivo evaluations are required to comprehensively assess their true therapeutic potential.