Circulation and biodistribution profiles of long-circulating PEG-liposomes of various sizes in rabbits
Circulation and biodistribution profiles of long-circulating PEG-liposomes of various sizes in rabbits
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DOI：
10.1016/s0378-5173(02)00703-2
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发表时间：
2003-03-06
影响因子：
5.8
通讯作者：
Phillips, WT
中科院分区：
文献类型：
--
作者：
Awasthi, VD;Garcia, D;Phillips, WT
为了确定可以保留由聚（乙二醇）-DSPE赋予的隐形行为的脂质体的最大尺寸，在兔中研究中性脂质体的循环和分布。通过挤出技术制备5种尺寸（136.2、165.5、209.2、275和318 nm）的脂质体（DSPC、胆固醇、PEG-DSPE和α-生育酚，90：80：4.5：3.9摩尔比），并用锝-99 m（Tc-99 m）进行放射性标记，以跟踪其在24 h内的分布。尽管所有脂质体在血液中显示出延长的循环，但在24 h时仍在循环中的量取决于它们的大小。随着脂质体尺寸的增加，脾脏中的放射性蓄积逐渐增加。在160-220 nm的粒径范围内，肝吸收最小，脾吸收中等，循环脂质体量最大。伽马照相机荧光照相术证实了尸检时脂质体的分布模式。1小时内的图像显示所有尺寸的脂质体的高血池活性。然而，在24 h时，275 nm的血池活性减弱，308 nm的脂质体的血池活性可忽略不计;较小尺寸的脂质体（136.2-209.2 nm）继续显示出高血池活性。对于136.2、165.5、209.2、275和318 nm脂质体，24 h时仍循环的放射性量分别为46.4、50.4、46.8、36.2和14.5%。相应的循环T（1/2）s分别为21.7、26.5、24.9、18.7和8.9 h。因此，PEG-脂质体在兔体内延长循环的最佳尺寸为160-220 nm。超过该范围，PEG-脂质体的隐形特性显著受损，并且分布的特征在于高RES积累。(C)2003 Elsevier Science B. V.保留所有权利。
To determine the largest size of liposomes that can retain stealth behavior conferred by poly(ethylene glycol)-DSPE, neutral liposomes were studied in rabbits for their circulation and distribution. Five sizes (136.2, 165.5, 209.2, 275 and 318 nm) of liposomes (DSPC, Cholesterol, PEG-DSPE and alpha-tocopherol, 90:80:4.5:3.9 molar ratio) were made by extrusion technique and radiolabeled with technetium-99m (Tc-99m) to follow their distribution through 24 h. Although all liposomes showed prolonged circulation in blood, the amount still in circulation at 24 h was dependent on their size. Radioactivity accumulation in spleen progressively increased with increase in size of the liposomes. In the size range of similar to 160-220 nm, liver uptake was minimum, spleen uptake was moderate while the amount of circulating liposomes was maximum. Gamma camera scintigraphy corroborated the distribution pattern of liposomes on necropsy. Images within 1 h showed high blood pool activities for liposomes of all sizes. However, at 24 h, the blood pool activity was diminished for 275 nm and negligible for 308 nm liposomes; the smaller sized liposomes (136.2-209.2 nm) continued to show high blood pool activity. The amounts of radioactivity still circulating at 24 h were 46.4,50.4,46.8, 36.2 and 14.5% for 136.2, 165.5, 209.2, 275 and 318 nm liposomes, respectively. Corresponding circulation T(1/2)s were 21.7, 26.5, 24.9, 18.7 and 8.9 h, respectively. Thus, the optimum size of PEG-liposomes for prolonged circulation in rabbits is 160-220 nm. Beyond this range, the stealth property of PEG-liposomes is significantly compromised and the distribution is characterized by high RES accumulation. (C) 2003 Elsevier Science B.V. All rights reserved.