Formulation of polymeric nanoparticles loaded sorafenib; evaluation of cytotoxicity, molecular evaluation, and gene expression studies in lung and breast cancer cell lines

Abstract

Sorafenib (SFB) is an anticancer drug with sparingly water solubility and reduced bioavailability. Nanoformulation of SFB can increase its dissolution rate and solubility. The current study aimed to formulate SFB in nanoparticles to improve their solubility. The sorafenib nanoparticles (SFB-PNs) were synthesized using the solvent evaporation method, then evaluated for their particle size, polydispersity index (PDI), zeta-potential, morphological structure, and entrapment efficiency (EE%). Further, the anticancer efficacy in A549 and Michigan Cancer Foundation-7 (MCF-7) cancer cell lines was evaluated. The SFB-NPs were uniform in size, which have 389.7 ± 16.49 nm, PDI of 0.703 ± 0.12, and zeta-potential of −13.5 ± 12.1 mV, whereas transmission electron microscopy showed a well-identified spherical particle. The EE% was found to be 73.7 ± 0.8%. SFB-NPs inhibited the cell growth by 50% after 48 h incubation, with IC50 of 2.26 and 1.28 µg/mL in A549 and MCF-7, respectively. Additionally, SFB-NPs showed a significant decrease (P < 0.05) in p21, and stathmin-1 gene expression levels in both cell lines. Moreover, SFB-NPs showed a significant increase in DNA damage of 25.50 and 26.75% in A549 and MCF-7, respectively. The results indicate that SFB-NPs are a potential candidate with an effective anticancer agent compared with free drugs.

Keywords

• sorafenib
• nanoparticles
• a549 cell lines
• mcf-7 cell lines
• anticancer activities