Encapsulating Anti-Parasite Benzimidazole Drugs into Lipid-Coated Calcium Phosphate Nanoparticles to Efficiently Induce Skin Cancer Cell Apoptosis

Abstract

Benzimidazole (BMZ) family of anti-worm drugs has been now repurposed as anti-cancer drugs. However, offering a general reformulation method for these drugs is essential due to their hydrophobicity and low aqueous solubility. In this work, we developed a general approach to load typical BMZ drugs as tiny nanocrystals within lipid-coated calcium phosphate (LCP) nanoparticles. BMZ drug-loaded LCP nanoparticles increased their solubility in PBS by 100–200% and significantly enhanced the anti-cancer efficacy in the treatment of B16F0 melanoma cells. These drug-LCP nanoparticles induced much more cancer cell apoptosis, generated much more reactive oxygen species (ROS) and inhibited Bcl-2 expression of cancer cells. Moreover, BMZ drug-loaded LCP nanoparticles caused morphological change and extension disruption of cancer cells, and significantly reduced migration activity, representing high possibility for inhibition of tumor dissemination and metastasis. Very advantageously, BMZ drug-loaded LCP nanoparticles did not show any obvious toxicity, Bcl-2 inhibition and morphological changes in HEK293T healthy cells. In conclusion, BMZ drug-incorporated LCP nanoformulations may be a valuable nanomedicine that is able to inhibit primary tumors and prevent tumor dissemination with minimum side effects on healthy cells and tissues.

Nanoparticle-Based Treatment Approaches for Skin Cancer: A Systematic Review

“…Mentha longiflora / Mentha pulegium -LNPs and Zataria multiflora -LNPs reduced cell viabilities to under 10% and 13%, respectively [ 46 , 47 ]. Benzimidazole-LNPs induced cancer cell apoptosis, generated reactive oxygen species, and inhibited Bcl-2 expression in cancer cells while sparing toxicity among healthy HEK293T cells [ 48 ]. In vivo murine studies were additionally conducted with plumbagin-loaded lipid–polymer hybrid NPs (LPNP) and TMZ-LNPs.…”

Investigation of benzimidazole anthelmintics as oral anticancer agents

“…Previous studies have shown that due to benzimidazole anthelmintic drug's poor solubility and low bioavailability, careful formulation strategy should be considered. 26 Although several formulation strategies were previously studied and proposed, 27,28 currently used benzimidazole anthelmintic drugs are orally administered for nonsystemic indications, but their pharmacokinetic parameters have not been fully reported. Based on fenbendazole and oxibendazole pharmacokinetic parameters, their increasing dose does not likely maintain the predose trough concentration (C trough ) for anticancer activities.…”

One–Pot Three–Component Synthesis of 2,4,5–Triaryl Imidazoles using Fe3O4@BisImid−CuBr Nanocomposite as an Ecofriendly and Efficient Magnetically Reusable Catalyst

“…Imidazole derivatives are a valuable class of nitrogen–containing heterocycles, whose synthesis and activities are always an attractive challenge among synthetic chemists [27–29] . Ketoconazole, miconazole and clotrimazole are imidazole derivatives and are widely used in the treatment of fungal infections [30–32] . Molecules containing imidazole ring are used to treat duodenal and gastric ulcers, gastroesophageal reflux disease, and associated symptoms such as heartburn and pain [33–35] .…”

“…[27][28][29] Ketoconazole, miconazole and clotrimazole are imidazole derivatives and are widely used in the treatment of fungal infections. [30][31][32] Molecules containing imidazole ring are used to treat duodenal and gastric ulcers, gastroesophageal reflux disease, and associated symptoms such as heartburn and pain. [33][34][35] Figure 1 shows several examples of important pharmaceutical and bioactive compounds that have an imidazole ring in their structure.…”