Pandey Rajesh, Khuller G K
Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh 160 012, India.
Tuberculosis (Edinb). 2005 Jul;85(4):227-34. doi: 10.1016/j.tube.2004.11.003.
The present study was planned to evaluate the chemotherapeutic potential of nebulized solid lipid particles (SLPs) incorporating rifampicin, isoniazid and pyrazinamide against experimental tuberculosis. The SLPs prepared by the "emulsion solvent diffusion" technique possessed a favourable mass median aerodynamic diameter suitable for bronchoalveolar drug delivery. Following a single nebulization to guinea pigs, therapeutic drug concentrations were maintained in the plasma for 5 days and in the organs (lungs, liver and spleen) for 7 days whereas free drugs were cleared by 1-2 days. The mean residence time and drug bioavailability were improved several-fold in the case of drug-loaded SLPs. A similar pharmacokinetic profile was observed in Mycobacterium tuberculosis-infected guinea pigs. On nebulization of drug-loaded SLPs to infected guinea pigs at every 7th day, no tubercle bacilli could be detected in the lungs/spleen after 7 doses of treatment whereas 46 daily doses of orally administered drugs were required to obtain an equivalent therapeutic benefit. Further, there was no evidence of any biochemical hepatotoxicity. Thus, nebulization of SLP-based antitubercular drugs forms a sound basis for improving drug bioavailability and reducing the dosing frequency for better management of pulmonary tuberculosis.
本研究旨在评估载有利福平、异烟肼和吡嗪酰胺的雾化固体脂质颗粒（SLP）对实验性结核病的化疗潜力。通过“乳液溶剂扩散”技术制备的SLP具有适合支气管肺泡给药的良好质量中位空气动力学直径。对豚鼠进行单次雾化后，血浆中的治疗药物浓度可维持5天，器官（肺、肝和脾）中的药物浓度可维持7天，而游离药物在1-2天内被清除。载药SLP的平均驻留时间和药物生物利用度提高了数倍。在感染结核分枝杆菌的豚鼠中也观察到了类似的药代动力学特征。每隔7天对感染豚鼠雾化载药SLP，在7剂治疗后，肺/脾中未检测到结核杆菌，而口服给药需要46剂每日剂量才能获得同等的治疗效果。此外，没有任何生化肝毒性的证据。因此，基于SLP的抗结核药物雾化给药为提高药物生物利用度和降低给药频率以更好地管理肺结核奠定了坚实基础。
