Application of Box-Behnken design in the optimization and development of albendazole-loaded zein nanoparticles as a drug repurposing approach for colorectal cancer management

Colorectal cancer (CRC) is the second cancer worldwide representing a major global health challenge. Numerous effective anticancer drugs have been developed in the last decade, yet the problem remains due to their low therapeutic index and nonspecificity. A new anticancer therapeutic paradigm is based on repurposing and nanoformulating drugs. Albendazole (ALB), a popular anthelmintic agent, was recently repurposed against CRC cells. In this study zein, an amphiphilic protein, was used to formulate nanoparticles (NPs) loaded with ALB. Box-Behnken design was selected to optimize the loaded NPs, the concentrations of polyvinyl alcohol, acetic acid, and the weight of zein were the independent variables. The dependent variables were the particle size, polydispersity index, and zeta potential. The optimized formula displayed a size of 84.3 ± 0.41 nm, PDI 0.13 ± 0.012, and a zeta potential of 42.5 ± 2.35 mV. ALB was successfully encapsulated into zein NPs and the release study revealed a desirable pH-responsive drug release behavior, that was negligible release during the first 2 h at pH 1.2 and progressive in the simulated colon environment reaching 71.1 ± 0.34 % at 6 h and 92.4 ± 1.11 % at 24 h. The anticancer effect of the loaded NPs on the human HCT116 cells showed favorable effects at 1 μM concentration with a significant decrease in the IC50 at days 2 and 3 upon loading albendazole into zein NPs. Zein nanoparticles proved to be prospective nanocarriers that could be used for the delivery of repurposed drugs in CRC treatment. •Colorectal cancer is a chief global health concern.•Drug repurposing is used to overcome the constraints of conventional anticancers.•Nanocarriers are promising systems to deliver repurposed drugs.•Zein is a protein, used in nanoparticles to deliver biologically active compounds.•Albendazole has anticancer properties in several human cancer cells.