Revisiting Niclosamide Formulation Approaches – a Pathway Toward Drug Repositioning

Mario Jug,1 Flavia Laffleur,2 Gioconda Millotti3 1Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, 10 000, Croatia; 2Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, 6020, Austria; 3Faculty of Natural Sciences, Juraj Dobrila University of Pula, Pula, 52100, CroatiaCorrespondence: Gioconda Millotti, Faculty of Natural Sciences, Juraj Dobrila University of Pula, Zagrebačka 30, Pula, 52100, Croatia, Email [email protected]: Niclosamide (NIC), an anthelmintic drug, has garnered recent attention for its potential as an antiviral, antibacterial, and chemotherapeutic agent, among other applications. Repurposing NIC presents a current trend, offering significant time and cost savings compared to developing entirely new therapeutic chemical entities. However, its drawback lies in poor solubility, resulting in notably low oral bioavailability. This review consolidates efforts to overcome this limitation by summarizing twelve categories of formulations, spanning derivatives, amorphous solid dispersions, co-crystals, nanocrystals, micelles, nanohybrids, lipid nanoparticles and emulsions, cyclodextrins, polymeric nanoparticles, dry powders for inhalation, 3D printlets, and nanofibers. These formulations cover oral, injectable, inhalable and potentially (trans)dermal routes of administration. Additionally, we present a comprehensive overview of NIC characteristics, including physico-chemical properties, metabolism, safety, and pharmacokinetics. Moreover, we identify gaps in formulation and administration pathways that warrant further investigation to address NIC poor bioavailability.Keywords: niclosamide, drug repurposing, solubility, formulations, administration pathways, pharmaco-kinetics