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Niclosamide, previously used as an anthelmintic drug is currently being repurposed for its anticancer activity. Niclosamide is a brick like biopharmaceutical classification system (BCS) class II drug with poor aqueous solubility and dissolution consequently leading to low bioavailability. By considering the physicochemical properties and geometry of niclosamide, inclusion complex with cyclodextrin was prepared by freeze drying method and characterized using FT-IR, DSC, PXRD, and 1 HNMR. In silico molecular modeling study was performed to study the possible interactions between niclosamide and cyclodextrin. The anticancer activity of niclosamide formulation was evaluated through in vitro cell cytotoxicity study using various cancer cell lines. The potential of niclosamide complex for improvement of the bioavailability was evaluated in male BALB/c mice. In vitro cytotoxicity studies indicated significantly higher cytotoxicity at lower concentrations and the pharmacokinetic studies showed significant improvement in C max and T max of niclosamide from cyclodextrin complex in comparison to pure niclosamide alone., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Niclosamide is a promising antitumor agent, but its low aqueous solubility places limit on its antitumor efficacy. The aim of this study was to improve the solubility and dissolution of niclosamide through using octenylsuccinate hydroxypropyl phytoglycogen (OHPP), an amphiphilic dendrimer-like biopolymer. The niclosamide-OHPP solid dispersion (niclo-OHPP SD) was prepared and characterized in terms of crystallinity, molecular interactions, solubility and dissolution profile, in-vitro antitumor efficacy, and in-vitro transdermal amount. X-ray powder diffraction analysis showed the amorphous state of niclosamide in niclo-OHPP SD. FTIR showed the formation of hydrogen bonding between niclosamide and OHPP. Solubility of niclosamide with niclo-OHPP SD was about 11,914 times that of niclosamide alone, and 61% of niclosamide with niclo-OHPP SD dissolved in 3 h upon dissolution. Against three cancer cell lines, cytotoxicity assays indicated greater inhibition by using niclo-OHPP SD than by using DMSO-assisted niclosamide solution. The cumulative transdermal amount of niclosamide with niclo-OHPP SD was 5.3 times that with niclosamide alone. This study showed that the use of OHPP could provide strong support for the development of niclosamide-based drug formulations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Despite standard cancer therapies such as chemotherapy and targeted therapy have shown some efficacies, the cancer in many cases eventually relapses and metastasizes upon stopping the treatment. There is a small subpopulation of cancer cells within tumor, with specific characters similar to those found in stem cells. This group of cancer cells is known as tumor-initiating or cancer stem cells (CSCs), which have an ability to self-renew and give rise to cancer cell progeny. CSCs are related with drug resistance, metastasis and relapse of cancer, hence emerging as a crucial drug target for eliminating cancer. Rapid advancement of CSC biology has enabled researchers to isolate and culture CSCs in vitro, making the cells amenable to high-throughput drug screening. Recently, drug repositioning, which utilizes existing drugs to develop potential new indications, has been gaining popularity as an alternative approach for the drug discovery. As existing drugs have favorable bioavailability and safety profiles, drug repositioning is now actively exploited for prompt development of therapeutics for many serious diseases, such as cancer. In this review, we will introduce latest examples of attempted drug repositioning targeting CSCs and discuss potential use of the repositioned drugs for cancer therapy.