Sustained release nanoformulations of second line antitubercular drugs levofloxacin and ethionamide had shown promise in pharmacokinetics and acute and sub-acute toxicity studies. The present study evaluated the clastogenicity potential of the nanoformulations of these antitubercular agents. Clastogenicity was evaluated by (a) in vitro micronucleus assay (b) in vivo micronucleus assay in Swiss albino mice and (c) sister chromatid exchange (SCE) in CHO cell lines. Ethionamide and levofloxacin loaded nanoparticles were 312 ± 64 nm and 245 ± 24 nm in size respectively and drug encapsulation was 35.2 ± 3.1% w/w and 45.6 ± 9.4% w/w, respectively. The frequency of MN-NCE/1000 NCE and MN-PCE/1000 PCE were significantly reduced in mice treated with ethionamide nanoparticle (3.5 ± 0.9, 13.8 ± 16.68) and levofloxacin nanoparticles (5.6 ± 2.7, 16.7 ± 12.7) compared to the mice treated with free ethionamide (11.5 ± 4.1, p = 0.23 and 45.19 ± 19.21, p = 0.38) and free levofloxacin (14.7 ± 1.88, p < 0.0001 and 54.6 ± 18.1, p = 0.0017), respectively. For in vitro, micronucleus assay frequencies of micronuclei per thousand bi-nucleated cells (MN-BN/1000 BN) was 188.3 ± 20.20 and 148 ± 20.42 for ethionamide and levofloxacin nanoparticles as compared to 232.6 ± 16.04 (p = 0.52) and 175 ± 5.56 (p = 0.45) for free ethionamide and levofloxacin, respectively. The average number of SCE per cell for nanoformulation of ethionamide were not different from that of free drug (4.9 ± 0.51 vs 4.1 ± 0.55, p = 0.86). The SCE per cells were not significant difference for nanoformulation of levofloxacin (2.33 ± 1.36 vs 5.46 ± 0.25, p = 0.88). In vitro and in vivo assays have shown relatively less clastogenic potential of equivalent dose of ethionamide nanoparticles as compared to the conventional formulation.

二线抗结核药物左氧氟沙星和乙硫异烟胺的缓释纳米制剂在药代动力学和急性和亚急性毒性研究中显示出前景。本研究评估了这些抗结核药物纳米制剂的致裂潜力。通过 (a) 体外微核试验 (b) 瑞士白化小鼠体内微核试验和 (c) CHO 细胞系中的姐妹染色单体交换 (SCE) 来评估致畸性。载有乙硫异烟胺和左氧氟沙星的纳米颗粒的大小分别为 312 ± 64 nm 和 245 ± 24 nm，药物包封率分别为 35.2 ± 3.1% w/w 和 45.6 ± 9.4% w/w。在用乙硫异烟胺纳米颗粒 (3.5 ± 0.9, 13.8 ± 16.68) 和左氧氟沙星纳米颗粒 (5.6 ± 2.7, 16.7 ± 12) 治疗的小鼠中，MN-NCE/1000 NCE 和 MN-PCE/1000 PCE 的频率显着降低。7) 与用游离乙硫异烟胺 (11.5 ± 4.1, p = 0.23 和 45.19 ± 19.21, p = 0.38) 和游离左氧氟沙星 (14.7 ± 1.88, p < 0.0001, p = 18.0, p = 18.0) 治疗的小鼠相比。为了在体外，对于乙硫异烟胺和左氧氟沙星纳米颗粒，每千个双核细胞中微核的微核检测频率 (MN-BN/1000 BN) 分别为 188.3 ± 20.20 和 148 ± 20.42，而乙硫异烟胺和左氧氟沙星纳米颗粒为 232.6 ± 16.04 (p = 5.52) ±50.55。 (p = 0.45) 分别为游离乙硫异烟胺和左氧氟沙星。乙硫异烟胺纳米制剂的每个细胞的平均 SCE 数与游离药物的 SCE 数没有区别（4.9 ± 0.51 vs 4.1 ± 0.55，p = 0.86）。对于左氧氟沙星的纳米制剂，每个细胞的 SCE 没有显着差异（2.33 ± 1.36 对 5.46 ± 0.25，p = 0.88）。与常规制剂相比，体外和体内试验表明，等效剂量的乙硫异烟胺纳米颗粒的致裂潜力相对较低。