LYMPHATIC TRANSPORT OF LIPOSOME-ENCAPSULATED AGENTS - EFFECTS OF LIPOSOME SIZE FOLLOWING INTRAPERITONEAL ADMINISTRATION
LYMPHATIC TRANSPORT OF LIPOSOME-ENCAPSULATED AGENTS - EFFECTS OF LIPOSOME SIZE FOLLOWING INTRAPERITONEAL ADMINISTRATION
复制标题
DOI：
10.1002/jps.2600740902
复制
发表时间：
1985-01-01
影响因子：
3.8
通讯作者：
HUNT, CA
中科院分区：
文献类型：
--
作者：
HIRANO, K;HUNT, CA
脂质体包封可以限制药物从腹膜给药部位进入血液，同时增强淋巴转运。我们评估了脂质体大小对腹腔给药后淋巴转运的影响。测试的脂质体具有0.72、0.46、0.17或0.048 μ m的平均直径和相同的组成。[14C]蔗糖是水性空间标记物（模型药物）。对胸导管插管大鼠给予剂量。随后的0 - 5小时的时间过程中的碳-14定量胸淋巴，几个淋巴结，血液和尿液。校准研究表明最大值为. apprx。30%的吸收剂量可在胸淋巴液中收集。各种淋巴结中的碳-14水平覆盖了1000倍的范围，在左纵隔、甲状旁腺、脑池和肾淋巴结中观察到相对较高的水平。脂质体在体内和体外的稳定性随着尺寸的减小而增加。腹腔吸收与大小无关。在淋巴中收集最小的脂质体，几乎没有淋巴结滞留。最大的脂质体被淋巴结保留得最多，如果需要增加淋巴和淋巴结内的治疗可用性，则将是该组的最佳原型载体。这些结果暗示了其他未经探索的物理和生理变量可能具有同等重要性。
Liposomal encapsulation can limit passage of a drug from a peritoneal administration site to blood, while enhancing lymphatic transport. We evaluated the effects of liposome size on lymphatic transport after intraperitoneal administration. Liposomes tested had mean diameters of either 0.72, 0.46, 0.17, or 0.048 .mu.m and identical compositions. [14C]Sucrose was the aqueous space marker (model drug), Doses were given to thoracic-duct-cannulated rats. The subsequent 0-5 h time-course of carbon-14 was quantified in thoracic lymph, several lymph nodes, blood, and urine. Calibration studies indicated a maximum of .apprx. 30% of the absorbed dose could be collected in thoracic lymph. Carbon-14 levels in the various nodes covered a 1000-fold range, and relatively high levels were observed in the left mediastinal, parathymic, cisternal, and renal lymph nodes. Liposome stability in vivo and in vitro increased with decreasing size. Absorption from the peritoneal cavity was independent of size. The smallest liposomes was collected in lymph with little lymph node retention. The largest liposomes were retained most by lymph nodes, and would be the best prototypical carrier of the group if increased therapeutic availability within both lymph and lymph nodes is desired. The results implicate other, unexplored physical and physiological variables as potentially of equal importance.