Anti-tumor effect of PEG-coated PLGA nanoparticles of febuxostat on A549 non-small cell lung cancer cells.

Abstract

In the present study, febuxostat (FBX)-loaded PEG-coated PLGA nanoparticles (FBX-PLGA-PEG) were developed and its anticancer activity on lung cancer cells was evaluated. FBX-PLGA-PEG were prepared by nanoprecipitation technique and characterized for particle size, size distribution, entrapment efficiency, and in vitro drug release study. The optimized formulations were used to evaluate cell viability, apoptosis, cell cycle, and caspase activity in A549 lung cancer cells. The optimized formulation showed spherical particle with average particle size of 180 ± 4.72nm, particle-size distribution 0.223 ± 0.003, entrapment efficiency (70 ± 2.56%), and drug release (99.1 ± 2.33%) at 12h. MTT cytotoxicity assay showed better cytotoxic potential of FBX-NPs than FBX solution against NSCLC A549 cells. The lower IC50 of FBX-NP (52.62 ± 2.52µg/mL) compared to FBX (68.0 ± 4.12µg/mL) are suggestive of a potential cytotoxic effect of nano-formulation compared to the drug itself. Furthermore, flow cytometry analysis showed significantly higher percentage of total apoptotic cells in FBX-NPs (10.38 ± 1.57%) as compared to FBX solution (2.76 ± 0.17%) showed strong proapoptotic potential of FBX nano-formulation. The increased caspase activity and percent of cells at G2/M phase of cell cycle increased for FBX nanoparticles were more effective than FBX solution in increasing caspase activity and percent of cells at G2/M phase of cell cycle. Our studies with FBX nanoparticles exhibited promising outcome which could be used as a strategies to combat lung cancer.