1. Formulation and evaluation of cyclodextrin complexes for improved anticancer activity of repurposed drug: Niclosamide
- Author
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Rahul B. Chavan, Sowjanya Thatikonda, Anurag Lodagekar, Naveen Chella, V.G.M. Naidu, Nalini R. Shastri, Roshan M. Borkar, and R. Srinivas
- Subjects
Male ,Drug ,Polymers and Plastics ,Drug Compounding ,media_common.quotation_subject ,Drug Evaluation, Preclinical ,Cmax ,Antineoplastic Agents ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Mice ,Pharmacokinetics ,Materials Chemistry ,medicine ,Animals ,Humans ,Cytotoxicity ,Niclosamide ,media_common ,chemistry.chemical_classification ,Cyclodextrins ,Mice, Inbred BALB C ,Cyclodextrin ,Chemistry ,Organic Chemistry ,Drug Repositioning ,Anticestodal Agents ,HCT116 Cells ,021001 nanoscience & nanotechnology ,In vitro ,0104 chemical sciences ,Bioavailability ,0210 nano-technology ,Nuclear chemistry ,medicine.drug - Abstract
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 1HNMR. 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 Cmax and Tmax of niclosamide from cyclodextrin complex in comparison to pure niclosamide alone.
- Published
- 2019