Soluções Eutécticas para Aperfeiçoamento Pulmonar Controlado e Avançado na Tuberculose

The ESCAPE-TB project presents a novel approach to enhance existing first-line anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) by using Deep Eutectic Solvents (DESs). This project investigates three distinct strategies: 1 - Therapeutic Deep Eutectic Solvents (THEDESs): These custom designed DESs incorporate a pharmaceutical drug, aiming to significantly improve its bioavailability and potentially decrease toxicity compared to conventional formulations. 2 - Natural Deep Eutectic Solvents (NADESs) for Solubility Enhancement: Recognizing limitations of current drugs, the project explores NADESs, DESs derived from natural ingredients, to improve the solubility and bioavailability of existing anti-tuberculosis drugs. 3 - Discovery of Novel Anti-TB NADESs: Beyond just improving solubility, the project seeks to identify NADESs exhibiting direct anti-TB activity, potentially leading to entirely new TB drugs. DESs enhance drug delivery, reduce interactions, and improve taste (potentially enabling lower doses, shorter treatments, and reduced side effects), promoting patient compliance (especially for children) and aiming to indirectly mitigate drug-resistant TB strains through improved treatment efficacy. Furthermore, the project incorporates nanotechnology through lipidic nanoparticles to encapsulate the DESs. This approach offers potential advantages: • Reduced potential DES toxicity: Encapsulation mitigate potential toxicity concerns. • Enhanced formulation stability: Nanoparticles protect the DESs, ensuring their efficacy throughout treatment. • Controlled drug release: Precise release optimize drug activity and minimize side effects. • Target-specific delivery: Nanoparticles can be designed to deliver drugs directly to infected cells, potentially improving treatment effectiveness. Targeting the four core TB drugs, the project tackles their shortcomings. DES formulations aim to be a one-stop solution, addressing Rifampicin's absorption issues, Ethambutol's compatibility challenges and long-term complications, Isoniazid's targeting limitations, Pyrazinamide's side effects. Extensive characterization, stability testing, and in-vitro efficacy evaluations are crucial to refine the developed formulations. The most promising candidate will then transition to in-vivo studies, laying the foundation for potential clinical applications. The ESCAPE-TB project envisions developing novel DES-based TB drug formulations, with at least one demonstrating compelling potential for in-vivo studies and eventual clinical application. This project carries the potential to: • Reduce the global burden of TB by improving treatment efficacy, compliance, and accessibility. • Improve patient outcomes and quality of life by reducing treatment duration, side effects, and long-term complications. • Reduce the development of drug-resistant TB by improving treatment efficacy and potentially reducing the selection pressure for resistant strains. • Promote sustainable drug development by utilizing potentially biodegradable and biocompatible DESs. • Facilitate global collaboration by fostering knowledge sharing and potential partnerships. This ambitious and innovative project holds significant promise for making a substantial contribution to the fight against TB by exploring a novel and potentially transformative approach to treatment.