Niclosamide loaded biodegradable chitosan nanocargoes: an in vitro study for potential application in cancer therapy

Abstract

Chitosan nanoparticles can advance the pharmacological and therapeutic properties of chemotherapeutic agents by controlling release rates and targeted delivery process, which eliminates the limitations of conventional anti-cancer therapies and they are also safe as well as cost-effective. The aim of present study is to explore the anti-tumour effect of niclosamide in lung and breast cancer cell lines using biocompatible and biodegradable carrier where nanoparticles loaded with hydrophobic drug (niclosamide) were synthesized, characterized and applied as a stable anti-cancer agent. Niclosamide loaded chitosan nanoparticles (Nic-Chi Np's) of size approximately 100–120 nm in diameter containing hydrophobic anti-cancer drug, i.e. niclosamide, were prepared. Physico-chemical characterization confirms that the prepared nanoparticles are spherical, monodispersed and stable in aqueous systems. The therapeutic efficacy of Nic-Chi Np's was evaluated against breast cancer cell line (MCF-7) and human lung cancer cell line (A549). MTT assay reveals the cell viability of the prepared Nic-Chi Np's against A549 and MCF-7 cells and obtained an IC50 value of 8.75 µM and 7.5 µM, respectively. Acridine orange/ethidium bromide dual staining results verified the loss of the majority of the cells by apoptosis. Flow cytometer analysis quantified the generation of intracellular reactive oxygen species (ROS) and signified that exposure to a higher concentration (2 × IC50) of Nic-Chi Np's resulted in elevated ROS generation. Notably, Nic-Chi Np treatment showed more apoptosis and cell death in MCF-7 as compared to A549. Further, the remarkable induction of apoptosis by Nic-Chi Np's was confirmed by semi-quantitative reverse transcription polymerase chain reaction, scanning electron microscopy and cell-cycle analysis. Thus, Nic-Chi Np's may have a great potential even at low concentration for anti-cancer therapy and may replace or substitute more toxic anti-mitotic drugs in the near future.

Enhanced antineoplastic/therapeutic efficacy using 5-fluorouracil-loaded calcium phosphate nanoparticles

“…Hoechst 33342 is a fluorescent DNA intercalating dye, which stains apoptotic cells or nuclei and yields blue florescence when bound to dsDNA in the cell nucleus [ 42 ] with excitation/emission wavelength at 352/455 nm. Rhodamine B, with an excitation/emission wavelength of 543/565 nm, provides a red fluorescence emission.…”

Host-targeted niclosamide inhibits C. difficile virulence and prevents disease in mice without disrupting the gut microbiota

“…In most cases, however, the low systemic exposure of niclosamide, which is likely a major contributor to its overall safety, has hampered its use for indications outside of the GI tract. Nevertheless, efforts have been undertaken to improve the bioavailability of niclosamide, using different salt forms, chemical modifications, and the use of nanoparticles 51 – 53 .…”

Amorphous Solid Dispersions and the Contribution of Nanoparticles to In Vitro Dissolution and In Vivo Testing: Niclosamide as a Case Study

“…Furthermore, the authors stated that any attempt to repurpose the previously approved niclosamide product as a cancer therapy should be avoided, and efforts should be directed toward developing analogs that have higher bioavailability [ 10 ]. The efforts to increase niclosamide’s bioavailability include the use of co-crystals [ 8 , 11 , 12 ], solid lipid nanoparticles [ 13 ], dendrimer-like materials [ 14 ], micelles [ 15 ], nanosuspensions [ 16 ], nanoparticles [ 17 ], lipid emulsions [ 18 ], and nanocrystals [ 19 ].…”