Galdopórpora Juan M, Martinena Camila, Bernabeu Ezequiel, Riedel Jennifer, Palmas Lucia, Castangia Ines, Manca Maria Letizia, Garcés Mariana, Lázaro-Martinez Juan, Salgueiro Maria Jimena, Evelson Pablo, Tateosian Nancy Liliana, Chiappetta Diego Andres, Moretton Marcela Analia
Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina.
Facultad de Ciencias Exactas y Naturales, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1113, Argentina.
Pharmaceutics. 2022 Apr 28;14(5):959. doi: 10.3390/pharmaceutics14050959.
Among respiratory infections, tuberculosis was the second deadliest infectious disease in 2020 behind COVID-19. Inhalable nanocarriers offer the possibility of actively targeting anti-tuberculosis drugs to the lungs, especially to alveolar macrophages (cellular reservoirs of the ). Our strategy was based on the development of a mannose-decorated micellar nanoformulation based in Soluplus to co-encapsulate rifampicin and curcumin. The former is one of the most effective anti-tuberculosis first-line drugs, while curcumin has demonstrated potential anti-mycobacterial properties. Mannose-coated rifampicin (10 mg/mL)-curcumin (5 mg/mL)-loaded polymeric micelles (10% /) demonstrated excellent colloidal properties with micellar size ~108 ± 1 nm after freeze-drying, and they remain stable under dilution in simulated interstitial lung fluid. Drug-loaded polymeric micelles were suitable for drug delivery to the deep lung with lung accumulation, according to the in vitro nebulization studies and the in vivo biodistribution assays of radiolabeled (99mTc) polymeric micelles, respectively. Hence, the nanoformulation did not exhibit hemolytic potential. Interestingly, the addition of mannose significantly improved (5.2-fold) the microbicidal efficacy against H37Rv of the drug-co-loaded systems in comparison with their counterpart mannose-free polymeric micelles. Thus, this novel inhaled nanoformulation has demonstrated its potential for active drug delivery in pulmonary tuberculosis therapy.
在呼吸道感染中，结核病是2020年仅次于COVID-19的第二大致命传染病。可吸入纳米载体为将抗结核药物主动靶向肺部，尤其是肺泡巨噬细胞（结核分枝杆菌的细胞储存库）提供了可能性。我们的策略基于开发一种以Soluplus为基础的甘露糖修饰胶束纳米制剂，用于共包封利福平和姜黄素。前者是最有效的一线抗结核药物之一，而姜黄素已显示出潜在的抗分枝杆菌特性。负载甘露糖包被利福平（10 mg/mL）-姜黄素（5 mg/mL）的聚合物胶束（10% /）冻干后胶束尺寸约为108±1 nm，具有优异的胶体性质，并且在模拟肺间质液稀释下保持稳定。根据体外雾化研究和放射性标记（99mTc）聚合物胶束的体内生物分布测定，载药聚合物胶束适合将药物递送至肺深部并在肺中蓄积。因此，该纳米制剂没有溶血潜力。有趣的是，与不含甘露糖的聚合物胶束相比，添加甘露糖显著提高了（5.2倍）药物共负载体系对H37Rv的杀菌效力。因此，这种新型吸入纳米制剂已证明其在肺结核治疗中进行主动药物递送的潜力。
