Revisiting Flubendazole Through Nanocrystal Technology: Statistical Design, Characterization and Its Potential Inhibitory Effect on Xenografted Lung Tumor Progression in Mice

Flubendazole (FLU) is a long-established antihelmintic drug that has been shown to exhibit promising activity against several cancer types, including lung cancer, which stands out for being aggressive and resistant to current therapies. In this work, we developed a new FLU nanocrystal through microfluidization followed by freeze-dried (FD) methods. By combining this method with statistical design, results revealed a significant influence of TPGS concentration on particle size reduction, favoring the achievement of the lowest mean particle size with superior performance and better physicochemical stability than polysorbate 80 and poloxamer 188. Also, thorough characterization analysis revealed the preparation methods did not interfere with the preservation of the drug structure, providing improved perspective on the therapeutic effect. Our preliminary in vivo study showed that FD–FLU-nanocrystal exhibits expressive ability to retard tumor progression and decreases the size of tumors of approximately 40% in A549R xenograft mouse model, when compared to the control group. This is the first development and optimization of a FLU nanocrystal, where results of preliminary in vivo study reinforce the great potential of this nanotechnology-based formulation to overcome FLU limitations, to be a new alternative for the cancer treatment.