Hunt C A, Rustum Y M, Mayhew E, Papahadjopoulos D
Drug Metab Dispos. 1979 May-Jun;7(3):124-8.
An extrusion technique was used to obtain multilamellar lipid vesicles (MLV, liposomes) of different size distribution. The larger MLV ranged in diameter from 0.1 to 2.6 mu and the smaller from 0.1 to 1.5 mu, and both were composed of phosphatidylserine/phosphatidylcholine/cholesterol in the molar ratio 1:4:5. After intravenous injection of large and small MLV containing encapsulated [3H]cytosine arabinoside (ara-C), their distribution in various organs showed that the fraction of the dose associated with lung was greater for large MLV relative to small MLV by factors of 3.6--10 after 1 hr, 5.3--14 after 4 hr, and 17--23 after 24 hr. For large MLV more than 50% of drug remaining in vivo after 24 hr was associated with the lung, compared with 2.5% for small MLV. Almost all of the 3H associated with lung at all times for both large and small MLV could be accounted for by unchanged ara-C. Differences in 3H levels between small and large MLV in other tissues were much less dramatic or were not significant. The apparent in vivo stability of the liposomes was not affected by size. The data are consistent with an initial trapping of large MLV during first passage in the lung, with subsequent binding and retention. Release of ara-C from large or small MLV in the lung is apparently slow relative to meatbolism.
采用挤压技术获得了不同尺寸分布的多层脂质体（MLV，脂质体）。较大的MLV直径范围为0.1至2.6μm，较小的为0.1至1.5μm，两者均由摩尔比为1:4:5的磷脂酰丝氨酸/磷脂酰胆碱/胆固醇组成。静脉注射含有包封的[3H]阿糖胞苷（ara-C）的大、小MLV后，它们在各器官中的分布表明，1小时后，与肺相关的剂量分数大MLV相对于小MLV高3.6至10倍，4小时后高5.3至14倍，24小时后高17至23倍。对于大MLV，24小时后体内残留的药物超过50%与肺相关，而小MLV为2.5%。大、小MLV在所有时间与肺相关的几乎所有3H都可由未变化的ara-C解释。其他组织中小MLV和大MLV之间的3H水平差异要小得多或不显著。脂质体在体内的表观稳定性不受尺寸影响。数据与大MLV在首次通过肺时最初被捕获，随后结合并滞留一致。相对于代谢，ara-C从肺中的大或小MLV释放显然较慢。
