Valiulin Sergey V, Onischuk Andrey A, Baklanov Anatoly M, Dubtsov Sergey N, Dultseva Galina G, An'kov Sergey V, Tolstikova Tatiana G, Belogorodtsev Sergey N, Schwartz Yakov Sh
Voevodsky Institute of Chemical Kinetics & Combustion, Russian Academy of Sciences, 630090 Novosibirsk, Russia.
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Antibiotics (Basel). 2022 Nov 1;11(11):1527. doi: 10.3390/antibiotics11111527.
The aerosol inhalation delivery of isoniazid in mice was investigated, and the specific activity of the aerosol form of isoniazid was studied with the mouse model of tuberculosis infection, the H37Rv strain. Aerosol delivery was performed using a laminar-flow horizontal nucleation chamber. The inhalation dose was measured in real-time mode using a diffusion aerosol spectrometer. The mean particle diameter was 0.6 ± 0.03 μm, and the inhalation dose was 5-9 mg/kg. Pharmacokinetic measurements were carried out in nose-only and whole-body chambers. Isoniazid concentration in blood serum and its mass in the lungs were measured as a function of time using high-performance liquid chromatography. Studies of the specific activity of aerosolized isoniazid reveal that treatment with the aerosol lead to the complete recovery of the experimental tuberculosis infection as early as after 28 days after the start of inhalation treatment, while in the animals from the group receiving isoniazid per-orally, sole revivable tuberculosis mycobacteria were detected. Histologic examinations show that only a few macrophagal (nonspecific) granulomas without mycobacteria were detected in the spleen after per-oral and aerosol treatment, the number of granulomas on the 28th day being three times smaller in the latter case. The results show that the developed technique of isoniazid aerosol inhalation may have clinical potential.
研究了异烟肼在小鼠中的气溶胶吸入给药情况，并使用结核感染小鼠模型H37Rv菌株研究了气溶胶形式异烟肼的比活性。使用层流水平成核室进行气溶胶给药。使用扩散气溶胶光谱仪以实时模式测量吸入剂量。平均粒径为0.6±0.03μm，吸入剂量为5 - 9mg/kg。在仅鼻和全身舱室中进行药代动力学测量。使用高效液相色谱法测量血清中异烟肼浓度及其在肺中的质量随时间的变化。雾化异烟肼比活性的研究表明，从吸入治疗开始后28天起，气溶胶治疗可使实验性结核感染完全恢复，而在口服异烟肼的组中，仅检测到可复活的结核分枝杆菌。组织学检查表明，口服和气溶胶治疗后，脾脏中仅检测到少数无分枝杆菌的巨噬细胞（非特异性）肉芽肿，在后一种情况下，第28天肉芽肿数量减少了三倍。结果表明，所开发的异烟肼气溶胶吸入技术可能具有临床潜力。
