β-Lactoglobulin-Modified Mesoporous Silica Nanoparticles: A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostate Cancer Cells

Maedeh Koohi Moftakhari Esfahani; Seyed Ebrahim Alavi; Peter J Cabot; Nazrul Islam; Emad L Izake

doi:10.3390/pharmaceutics14040884

β-Lactoglobulin-Modified Mesoporous Silica Nanoparticles: A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostate Cancer Cells

Pharmaceutics. 2022 Apr 18;14(4):884. doi: 10.3390/pharmaceutics14040884.

Authors

Maedeh Koohi Moftakhari Esfahani^{1

2}, Seyed Ebrahim Alavi³, Peter J Cabot⁴, Nazrul Islam^{5

6}, Emad L Izake^{1

2}

Affiliations

¹ School of Chemistry and Physics, Faculty of Science, Queensland University of Technology (QUT), 2 George Street, Brisbane, QLD 4000, Australia.
² Centre for Materials Science, Queensland University of Technology (QUT), 2 George Street, Brisbane, QLD 4000, Australia.
³ School of Medicine and Dentistry, Griffith University, Gold Coast, QLD 4215, Australia.
⁴ School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia.
⁵ School of Clinical Sciences, Faculty of Health, Queensland University of Technology, 2 George Street, Brisbane, QLD 4000, Australia.
⁶ Centre for Immunology and Infection Control (CIIC), Queensland University of Technology, Brisbane, QLD 4000, Australia.

Abstract

The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility and bioavailability. In this study, Mobil Composition of Matter Number 48 (MCM-48) nanoparticles were synthesized and functionalized with succinylated β-lactoglobulin (BLG) to prevent early-burst drug release. The BLG-modified amine-functionalized MCM-48 (MCM-BLG) nanoparticles were loaded with FBZ to produce the drug nanoformulation (FBZ-MCM-BLG) and improved the water solubility and, consequently, its anticancer effects against human prostate cancer PC-3 cells. The prepared FBZ-MCM-BLG was characterized in terms of size, zeta potential, drug loading capacity, morphology, thermal and chemical analyses, drug release, cellular uptake, cell viability, cell proliferation, production of reactive oxygen species (ROS), and cell migration. The results demonstrated that the FBZ-MCM-BLG nanoparticles have a spherical morphology with a size and zeta potential of 369 ± 28 nm and 28 ± 0.4 mV, respectively. The drug loading efficiency of the new nanoformulation was 19%. The release of FBZ was pH-dependent; a maximum cumulative release of about 76 and 62% in 12 h and a burst release of 53 and 38% in the first 0.5 h was observed at pH 1.2 and 6.8, respectively. The prepared FBZ-MCM-BLG formulation demonstrated higher cytotoxicity effects against PC-3 cells by 5.6- and 1.8-fold, respectively, when compared to FBZ and FBZ-MCM nanoparticles. The new formulation also increased the production of ROS by 1.6- and 1.2-fold and inhibited the migration of PC-3 cells when compared to the FBZ and FBZ-MCM nanoparticles, respectively. Overall, FBZ-MCM-BLG nanoparticles improved FBZ delivery to PC-3 cells and have the potential to be evaluated for the treatment of prostate cancer following a comprehensive in vivo study.

Keywords: anthelmintic; fenbendazole; mesoporous silica nanoparticle; prostate cancer.