Insights into therapeutic liquid mixtures and formulations towards tuberculosis therapy

Santos, Filipa; Pires, David; Anes, Elsa; Duarte, Ana Rita C.

http://hdl.handle.net/10362/154569

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Therapeutic liquid mixtures, as deep eutectic systems, are considered a sustainable strategy that can be useful for the modification and enhancement of the pharmacokinetics and pharmacodynamics of different active ingredients. In this study, we assessed the stability and antibacterial activity of therapeutic liquid formulations prepared with anti-tuberculosis drugs. Tuberculosis therapy presents various pitfalls related, for example, to the administration of prolonged regimens of multiple drugs, different severe adverse effects, low compliance of the patient to treatment and the development of drug resistance. During this study, it was possible to assess the physicochemical stability of the formulations for 6 months, by polarized optical microscopy, 1H NMR and FTIR-ATR. Furthermore, the mixtures present an antibacterial effect against a drug-susceptible Mycobacterium tuberculosis strain (H37Rv). This was particularly evident for the mixtures with ethambutol incorporated, making them interesting to pursue with further studies and evaluation of clinical applicability. Upon infection, it was also observed that a single and higher dose appears to be more effective than lower separate doses, which could allow the production of patient-friendly formulations.

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Funding Information: This project has received funding from the European Union’s Horizon 2020 (European Research Council) under grant agreement No ERC-2016-CoG 725034 and was supported by the Associate Laboratory for Green Chemistry-LAQV. We also thank the support of ADEIM-FFUL (Associação para o Ensino e a Investigação em Microbiologia). Publisher Copyright: © 2023 The Author(s)