Obinu Antonella, Porcu Elena Piera, Piras Sandra, Ibba Roberta, Carta Antonio, Molicotti Paola, Migheli Rossana, Dalpiaz Alessandro, Ferraro Luca, Rassu Giovanna, Gavini Elisabetta, Giunchedi Paolo
Department of Chemistry and Pharmacy, University of Sassari, via Muroni 23/a, 07100 Sassari, Italy.
Department of Biomedical Sciences, University of Sassari, Viale San Pietro, 07100 Sassari, Italy.
Pharmaceutics. 2020 Nov 24;12(12):1132. doi: 10.3390/pharmaceutics12121132.
The role of mycobacterial efflux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential efflux inhibitor has been demonstrated. In this work, the chemical-physical properties of the SS13 were investigated; furthermore, a formulative study aimed to develop a formulation suitable for oral administration was performed. SS13 shows nonintrinsic antitubercular activity, but it increases the antitubercular activity of all the tested drugs on several strains. SS13 is insoluble in different simulated gastrointestinal media; thus, its oral absorption could be limited. Solid lipid nanoparticles (SLNs) were, therefore, developed by using two different lipids, Witepsol and/or Gelucire. Nanoparticles, having a particle size (range of 200-450 nm with regards to the formulation composition) suitable for intestinal absorption, are able to load SS13 and to improve its permeation through the intestinal mucosa compared to the pure compound. The cytotoxicity is influenced by the concentration of nanoparticles administered. These promising results support the potential application of these nanocarriers for increasing the oral permeation of SS13 in multidrug-resistant tuberculosis management.
分枝杆菌外排泵在耐多药结核病中的作用已被广泛报道。最近，一种名为SS13的新化合物已被合成，并证明了其作为潜在外排抑制剂的活性。在这项工作中，对SS13的化学物理性质进行了研究；此外，还进行了一项配方研究，旨在开发一种适合口服给药的制剂。SS13本身没有抗结核活性，但它能增强所有受试药物对几种菌株的抗结核活性。SS13在不同的模拟胃肠介质中不溶；因此，其口服吸收可能受到限制。因此，使用两种不同的脂质Witepsol和/或Gelucire制备了固体脂质纳米粒（SLN）。纳米粒的粒径（根据制剂组成，范围为200-450nm）适合肠道吸收，与纯化合物相比，能够负载SS13并改善其透过肠黏膜的渗透。细胞毒性受纳米粒给药浓度的影响。这些有前景的结果支持了这些纳米载体在耐多药结核病治疗中增加SS13口服渗透性的潜在应用。
