Vale Nuno, Correia Alexandra, Silva Sara, Figueiredo Patrícia, Mäkilä Ermei, Salonen Jarno, Hirvonen Jouni, Pedrosa Jorge, Santos Hélder A, Fraga Alexandra
UCIBIO/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal.
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Bioorg Med Chem Lett. 2017 Feb 1;27(3):403-405. doi: 10.1016/j.bmcl.2016.12.060. Epub 2016 Dec 26.
Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv. The activity of the conjugate was increased when compared to free-ETH, which suggests that the nature of the synergy between the NPs and ETH is likely due to the weakening of the bacterial cell wall that improves conjugate-penetration. These ETH-conjugated NPs have great potential in reducing dosing frequency of ETH in the treatment of multidrug-resistant tuberculosis (MDR-TB).
乙硫异烟胺（ETH）是一种重要的二线抗结核药物，用于治疗耐多药结核分枝杆菌感染的患者。最近，我们报道将ETH负载到热碳化多孔硅（TCPSi）纳米颗粒中可提高ETH在不同pH值下的溶解度和渗透性，并增强其代谢过程。基于这些结果，我们合成了与ETH共轭的羧酸功能化热烃化多孔硅纳米颗粒（UnTHCPSi NPs），并评估了其对结核分枝杆菌H37Rv菌株的抗菌效果。与游离ETH相比，共轭物的活性有所提高，这表明纳米颗粒与ETH之间协同作用的性质可能是由于细菌细胞壁的弱化，从而提高了共轭物的渗透性。这些ETH共轭纳米颗粒在降低耐多药结核病（MDR-TB）治疗中ETH的给药频率方面具有巨大潜力。
