PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells.

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

doi:10.3390/pharmaceutics13101605

Maedeh Koohi Moftakhari Esfahani, Emad L Izake + Show 3 more

Open Access

https://doi.org/10.3390/pharmaceutics13101605

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Abstract

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.

Highlights

Despite high investment in pharmaceutical research and related technologies in past decades, the failure rate of drug candidates during their phase I clinical trials is approximately 90%, and it usually takes billions of dollars and 10–15 years to develop a new drug [1]
Drug repurposing is very helpful in the process of drug development when compared to the traditional de novo processes used for drug discovery [3]
This study aimed to encapsulate FBZ as a repurposed and hydrophobic drug into Mesoporous silica nanoparticles (MSNPs) to improve its properties against prostate cancer PC-3 cells

Summary

Introduction

Despite high investment in pharmaceutical research and related technologies in past decades, the failure rate of drug candidates during their phase I clinical trials is approximately 90%, and it usually takes billions of dollars and 10–15 years to develop a new drug [1]. Drug repurposing has received considerable attention from the pharmaceutical industry and research community for drug discovery [2]. Drug repurposing is very helpful in the process of drug development when compared to the traditional de novo processes used for drug discovery [3]. The repurposing of anthelmintics (e.g., fenbendazole (FBZ)) for the treatment of cancer has received considerable attention [4,5,6]

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