Fielding R M, Abra R M
Liposome Technology, Inc., Menlo Park, California 94025.
Pharm Res. 1992 Feb;9(2):220-3. doi: 10.1023/a:1018989423909.
Maximum duration of bronchodilator efficacy in inhaled liposome-based formulations depends on optimizing the in vivo release rate of the encapsulated bronchodilator. We investigated the effect of several formulation variables on the pulmonary residence time of 3H-terbutaline sulfate liposomes administered intratracheally in guinea pigs, using an improved method enabling the measurement of pulmonary drug absorption for extended periods of time in conscious animals. Half-lives of liposome-encapsulated 3H-terbutaline disappearance from the lungs and airways after instillation ranged from 1.4 to 18 hr and were markedly affected by liposome size, cholesterol content, and phospholipid composition. This study demonstrates that liposomes can significantly prolong the residence time of bronchodilators in the lungs and that precise control over the pulmonary residence time of encapsulated bronchodilators can be achieved by controlling formulation variables.
基于吸入脂质体的制剂中支气管扩张剂疗效的最长持续时间取决于优化包封的支气管扩张剂的体内释放速率。我们使用一种改进的方法，该方法能够在清醒动物中长时间测量肺部药物吸收，研究了几个制剂变量对豚鼠气管内给予的³H-硫酸特布他林脂质体肺部滞留时间的影响。滴注后，脂质体包封的³H-硫酸特布他林从肺和气道消失的半衰期为1.4至18小时，并受到脂质体大小、胆固醇含量和磷脂组成的显著影响。这项研究表明，脂质体可以显著延长支气管扩张剂在肺部的滞留时间，并且通过控制制剂变量可以实现对包封的支气管扩张剂肺部滞留时间的精确控制。
