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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 gmillotti@unipu.hrAbstract: 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

Background: Tick-borne diseases, caused by bacterial pathogens, pose a growing threat to public health in Europe. This paper provides an overview of the historical context of the discovery of the most impactful pathogens transmitted by ticks, including Borrelia burgdorferi sensu lato, Rickettsia spp., Anaplasma spp., Francisella spp., Ehrlichia spp., and Neoehrlichia mikurensis. Understanding the historical context of their discovery provides insight into the evolution of our understanding of these pathogens., Methods and Results: Systematic investigation of the prevalence and transmission dynamics of these bacterial pathogens is provided, highlighting the intricate relationships among ticks, host organisms, and the environment. Epidemiology is explored, providing an in-depth analysis of clinical features associated with infections. Diagnostic methodologies undergo critical examination, with a spotlight on technological advancements that enhance detection capabilities. Additionally, the paper discusses available treatment options, addressing existing therapeutic strategies and considering future aspects., Conclusions: By integrating various pieces of information on these bacterial species, the paper aims to provide a comprehensive resource for researchers and healthcare professionals addressing the impact of bacterial tick-borne diseases in Europe. This review underscores the importance of understanding the complex details influencing bacterial prevalence and transmission dynamics to better combat these emerging public health threats., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)