12.11.2024
Inhaled liposomal bedaquilin: A new nanomedicine in the fight against tuberculosis?
Researchers from the joint project “ANTI-TB” were able to show that the efficacy of bedaquiline - an important antibiotic in the fight against multidrug-resistant tuberculosis (MDR.TB) - could be improved when the active ingredient was coupled to special nanostructures and transported directly into the lungs by inhalation.
Tuberculosis is globally the most important infectious disease caused by bacteria. The treatment of tuberculosis is made much more difficult by the alarming increase in cases caused by antibiotic-resistant pathogens. Nanomedicines could increase the effectiveness of new drugs against pulmonary tuberculosis. In a recently published study in the journal ACS Infectious Diseases scientists from the ANTI-TB consortium discovered that liposomal bedaquiline, when delivered to the lung, has the potential to improve the pharmacokinetic profile of the drug compared to a conventional oral form. This shift in drug pharmacokinetics could favorably improve the therapeutic efficacy of this second-line TB drug, by increasing drug concentrations in the lung where they are needed to combat the disease.
The research, funded by the BMBF, posed the question of whether novel nanomedicine based drug formulations, like liposomes, could better reach the pulmonary infectious foci and increase drug amounts in the lung when applied via inhalation. The liposomal formulation is required to help keep the drug in the lung at higher concentrations, while at the same time reducing drug-associated side effects in other parts of the body, such as the heart. The study results suggested that this was indeed the case. Lipsomal bedaquiline applied directly to the lung showed higher lung concentrations, an improved antibacterial effect and also lower levels of the drug metabolite, N-desmethyl-bedaquiline, in the blood, especially when compared to the drug given orally. Since higher metabolite concentrations are associated with higher risks of cardiac side effects, the new therapeutic approach could expand the therapy with bedaquiline to patients who are at risk for these specific adverse effects. At the same time, the inhaled liposomal treatment may even improve the therapeutic effect compared to tablets, although further studies over longer treatment periods are required to confirm this. This is why the research team now hopes to build on these exciting findings by applying for further funding to expand their nanomedicine approach by assessing inhaled liposomal bedaquiline in the context of tuberculosis therapy.
Publication:
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Marwitz F, Hädrich G, Redinger N, Besecke KFW, Li F, Aboutara N, Thomsen S, Cohrs M, Neumann PR, Lucas H, Kollan J, Hozsa C, Gieseler RK, Schwudke D, Furch M, Schaible U, Dailey LA. Intranasal Administration of Bedaquiline-Loaded Fucosylated Liposomes Provides Anti-Tubercular Activity while Reducing the Potential for Systemic Side Effects. ACS Infect Dis. 2024 Sep 13;10(9):3222-3232. doi: 10.1021/acsinfecdis.4c00192
Further Informationen:
- Antibiotika Nanocarrier zur therapeutischen Inhalation gegen Tuberkulose; https://www.gesundheitsforschung-bmbf.de/de/antibiotika-nanocarrier-zur-therapeutischen-inhalation-gegen-tuberkulose-anti-tb-7432.php:
