Brigatinib loaded poly(d,l-lactide-co-glycolide) nanoparticles for improved anti-tumoral activity against non-small cell lung cancer cell lines

Abstract

Objective

The aim of the current investigation was to develop poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to sustain the brigatinib (BTB) release for prolong time period and to examine the antitumor effect of the optimized NPs.

Significance

Optimized PLGA-based NPs of BTB could be potentially used as a promising nanocarrier for the treatment of non-small cell lung cancer.

Methods

BTB-loaded NPs were fabricated with core-shell of PLGA by solvent evaporation technique using different proportions of PLGA polymer and poly-vinyl alcohol (PVA) stabilizer. The prepared NPs were evaluated for particle characterizations; size, polydispersity index (PDI), zeta-potential, entrapment efficiency (EE), and drug loading (DL), Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction studies. The optimized NPs (BN5) were further evaluated for morphology, stability, and cytotoxicity studies against A549 cell-lines.

Results

Among the nine different NPs formulae (BN1–BN9), BN5 was optimized with composition of BTB (30 mg), PLGA (75 mg), PVA (0.55% w/v), represents an average particle size of (267.1 ± 1.01 nm), PDI (0.101 ± 0.007), and zeta potential (–42.1 ± 0.75 mV), high EE (66.83 ± 0.06%), and DL (6.17 ± 0.69%). SEM image of selected NPs was spherical with smooth surface. In vitro drug release profile in phosphate buffers (pH 5 and pH 7.4) showed a biphasic release with initial burst phase followed by sustained release for prolong time. Furthermore, optimized NPs (BN5) exhibited excellent cytotoxic activity against A549 cell-lines with IC₅₀ value of 5.25 ± 0.23 µg/mL.

Conclusion

The overall results suggest that BTB-loaded PLGA NPs could be a potential nanocarrier for lung cancer treatment.

Keywords:

• A549
• brigatinib
• nanoparticles
• NSCLC
• PLGA

Disclosure statement

The authors involved in the research hereby declare that there is no conflict of interests.

Additional information

Funding

This research publication was supported by the Deanship of Scientific Research (DSR) at Prince Sattam Bin Abdulaziz University (PSAU), Al-Kharj, Saudi Arabia.