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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Pulmonary disposition of vancomycin nebulized as lipid vesicles in rats
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Pulmonary disposition of vancomycin nebulized as lipid vesicles in rats

机译：雾化成大鼠脂质囊泡的万古霉素的肺处置

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Formulation of antibiotics as inhalable products is proposed to improve their therapeutic index when intended for the treatment of pulmonary infections; as vancomycin shows reduced values of lung partition coefficient, pulmonary administration might be an interesting alternative to conventional administration routes. An experimental study has been performed to compare the pulmonary disposition of vancomycin after inhalation of the drug formulated as a solution and as lipid vesicles (conventional liposomes or liposomes modified with chitosan). Vancomycin concentrations were determined in bronchoalveolar fluid, pulmonary tissue and blood samples from 27 Wistar rats distributed in three groups subjected to nebulisation of the drug formulated as a solution, conventional liposomes or chitosomes. Statistically significant differences between the mean drug concentrations in bronchoalveolar lavage (BALF) and lung tissue were found upon comparing the solution to lipid vesicles (116.95 μg ml-1 ±62.13 versus 68.34 μg ml-1 ±28.90 for liposomes and 65.36±22.11 μg g-1 for chitosomes in BALF; 222.74±37.15 μg g-1 versus 357.17±65.37 μg g-1 for liposomes and 378.83±85.87 μg g-1 for chitosomes in pulmonary tissue). The amount of available drug estimated by mass balance reached the highest values for chitosomes followed by liposomes (24289.66±4795.48 μg and 20207.91±5318.29 μg, respectively) and the lowest for the solution (18971.64±4765.38 μg). The drug transport and tissue uptake processes showed to be dependent on the nebulized formulation, being facilitated by the lipid vesicles that improved drug passage from the airway space to the pulmonary tissue and systemic circulation.
机译：当打算用于治疗肺部感染时，建议将抗生素配制成可吸入产品，以提高其治疗指数。由于万古霉素显示肺分配系数值降低，因此肺部给药可能是常规给药途径的有趣替代方法。进行了一项实验研究，比较了吸入配制为溶液和脂质囊泡（常规脂质体或壳聚糖修饰的脂质体）的药物后万古霉素在肺部的分布。测定了来自27只Wistar大鼠的支气管肺泡液，肺组织和血液样本中的万古霉素浓度，这些大鼠分布在三组中，经过雾化处理制成溶液，常规脂质体或壳聚糖的药物。通过将溶液与脂质囊泡进行比较，发现支气管肺泡灌洗液（BALF）和肺组织中平均药物浓度之间存在统计学上的显着差异（脂质体分别为116.95μgml-1±62.13和68.34μgml-1±28.90，脂质体为65.36±22.11μg BALF中的壳聚糖为-1;脂质体为227.74±37.15μgg-1，脂质体为357.17±65.37μgg-1，肺组织中壳状体为378.83±85.87μgg-1）。通过质量平衡估算的可用药物量达到最高的是壳聚糖，其次是脂质体（分别为24289.66±4795.48μg和20207.91±5318.29μg），而溶液的最低值（18971.64±4765.38μg）。药物运输和组织吸收过程显示出依赖于雾化制剂，脂质囊泡促进了药物从气道空间到肺组织和全身循环的通过，从而促进了药物的运输和组织吸收。

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