Oku N
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Shizuoka, Japan
Adv Drug Deliv Rev. 1999 Apr 5;37(1-3):53-61. doi: 10.1016/s0169-409x(98)00110-0.
Liposomes encapuslating positron emitters are applicable for diagnostic imaging and are useful to investigate the real-time liposomal trafficking in vivo. Long-circulating liposomes encapsulaing [2-(18)F]-2-fluoro-2-deoxyglucose were administrated to tumor-bearing mice, and a PET scan was performed. Small-sized long-circulating liposomes (100 nm) tended to accumulate in tumor tissues of tumor-bearing mice as compared with conventional liposomes. Then the size effect on trafficking of long-circulating liposomes was investigated. Large-sized liposomes (>300 nm) accumulated in liver and spleen in a time dependent manner. On the contrary, small-sized ones (<200 nm) were transiently accumulated in the liver right after injection, but the accumulation decreased time dependently, suggesting that, although the majority of small long-circulating liposomes remain in bloodstream, some extravasate once into interstitial spaces in liver which re-enter into bloodstream again. Next the trafficking of so-called long-circulating liposomes, i.e., liposomes modified with ganglioside GM1, palmityl glucuronide (PGlcUA), and polyethylene glycol (PEG), in tumor-bearing mice was examined. The accumulation of all three kinds of long-circulating liposomes in liver decreased time-dependently, and PGlcUA-liposomes could avoid liver-trapping the most efficiently. Tumor accumulation of liposomes was obvious for PGlcUA-liposomes and PEG-liposomes from immediately after injection, but not for GM1-liposomes. Finally, the trafficking of differently charged liposomes was investigated in normal mice. The accumulation of positively charged liposomes containing 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl bromide was different from that of neutral and negatively charged DCP-liposomes. The agglutinability of and serum protein ginding to positively charged liposomes were marked, suggesting that these factors affect the high accumulation of DMRIE-liposomes in liver. Non-invasive PET analysis of liposomal trafficking is beneficial for obtaining information about liposomal drug delivery, and long-circulating liposomes might be useful for diagnostic tumor imaging by PET.
包裹正电子发射体的脂质体可用于诊断成像，有助于研究体内脂质体的实时运输情况。将包裹[2-(18)F]-2-氟-2-脱氧葡萄糖的长循环脂质体注射到荷瘤小鼠体内，并进行正电子发射断层扫描（PET扫描）。与传统脂质体相比，小尺寸的长循环脂质体（100纳米）倾向于在荷瘤小鼠的肿瘤组织中积累。随后研究了长循环脂质体大小对其运输的影响。大尺寸脂质体（>300纳米）以时间依赖性方式在肝脏和脾脏中积累。相反，小尺寸脂质体（<200纳米）在注射后立即在肝脏中短暂积累，但积累量随时间下降，这表明，虽然大多数小的长循环脂质体留在血液中，但有些会一旦渗入肝脏的间质空间，然后再次进入血液。接下来，研究了所谓的长循环脂质体，即经神经节苷脂GM1、棕榈酰葡糖醛酸（PGlcUA）和聚乙二醇（PEG）修饰的脂质体在荷瘤小鼠体内的运输情况。所有三种长循环脂质体在肝脏中的积累均随时间下降，且PGlcUA-脂质体最有效地避免了肝脏捕获。PGlcUA-脂质体和PEG-脂质体在注射后立即在肿瘤中的积累明显，但GM1-脂质体则不然。最后，在正常小鼠中研究了不同电荷脂质体的运输情况。含有1,2-二肉豆蔻酰氧基丙基-3-二甲基羟乙基溴的带正电荷脂质体的积累与中性和带负电荷的DCP-脂质体不同。带正电荷脂质体的凝集性和与血清蛋白的结合很明显，这表明这些因素影响了DMRIE-脂质体在肝脏中的高积累。脂质体运输的非侵入性PET分析有利于获取有关脂质体药物递送的信息，长循环脂质体可能对PET诊断肿瘤成像有用。
