Gilbert B E, Six H R, Wilson S Z, Wyde P R, Knight V
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.
Antiviral Res. 1988 Sep;9(6):355-65. doi: 10.1016/0166-3542(88)90037-x.
Enviroxime inhibits the replication of all rhinoviruses tested in vitro at very low concentrations (10-100 ng/ml), but evaluations in humans have not consistently shown efficacy. Lack of an appropriate method for administering this water-insoluble drug may have contributed to the latter result. The present report describes the characteristics and utilization of small particle aerosols to continuously deliver enviroxime-containing liposomes (LE) throughout the respiratory tract. The enviroxime content of liposomes and biological fluids of exposed individuals was quantified by high performance liquid chromatography using C18 resin, a mobile phase of 60:40 acetonitrile:water, and monitoring at 215 nm. Small particle aerosols of LE generated by Puritan-Bennett nebulizers had mass median diameters ranging from 2.4 to 3.1 microns. The concentration of enviroxime in aerosol particles was proportional to the reservoir concentration; during the first hour of operation, the mean concentration was 20 micrograms of enviroxime/l of aerosol. Liposome particles in the reservoir, although initially heterogeneous in size (less than 0.1 to greater than 1 micron), were processed by passage through the nebulizer to smaller, more homogeneous particles; the majority were less than 0.2 micron. In a preliminary study to evaluate short term tolerance and toxicity, five volunteers were exposed to small particle aerosol of LE for 1 h. At 1 h post-treatment, large amounts of enviroxime were still present in the nasal wash as determined both by HPLC and biological assay. Enviroxime was not detected in any urine sample and was detected in only 1 of 5 serum samples. No side effects were noted. This data suggest that liposome aerosols offer a method for the delivery of hydrophobic compounds for the treatment of respiratory diseases.
恩韦肟在极低浓度（10 - 100纳克/毫升）下就能抑制体外测试的所有鼻病毒的复制，但人体试验结果并不一致显示其有效。缺乏合适的给药方法可能是导致这一结果的原因。本报告描述了小颗粒气雾剂的特性及应用，其可在整个呼吸道持续递送含恩韦肟的脂质体（LE）。使用C18树脂、60:40乙腈:水的流动相并在215纳米处监测，通过高效液相色谱法定量脂质体和暴露个体生物体液中的恩韦肟含量。普里坦-贝内特雾化器产生的LE小颗粒气雾剂的质量中值直径为2.4至3.1微米。气雾剂颗粒中恩韦肟的浓度与储库浓度成正比；在操作的第一个小时内，平均浓度为20微克恩韦肟/升气雾剂。储库中的脂质体颗粒虽然最初大小不均一（小于0.1至大于1微米），但通过雾化器处理后变成了更小、更均匀的颗粒；大多数颗粒小于0.2微米。在一项评估短期耐受性和毒性的初步研究中，五名志愿者暴露于LE小颗粒气雾剂中1小时。治疗后1小时，通过高效液相色谱法和生物测定法均确定鼻洗液中仍存在大量恩韦肟。在任何尿液样本中均未检测到恩韦肟，仅在5份血清样本中的1份中检测到。未观察到副作用。这些数据表明脂质体气雾剂为递送用于治疗呼吸道疾病的疏水化合物提供了一种方法。
