Wright K C, Kasi L P, Jahns M S, Hashimoto S, Wallace S
Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Radiology. 1990 Sep;176(3):691-4. doi: 10.1148/radiology.176.3.2389028.
In an effort to improve hepatic uptake of liposomes for drug delivery, empty vesicles were administered by means of selective arterial infusion. Negatively charged, multilamellar liposomes were labeled with technetium-99m and infused into healthy adult dogs. Each dog received 100 mg/m2 of lipid over 10 minutes at 2 mL/min. Liposomes were administered via the common hepatic artery after proximal occlusion of the gastroduodenal artery, via the cranial mesenteric artery, and via the cephalic vein. Distribution (liver, spleen, and lungs) was determined by computer-assisted external imaging techniques. On the average, after arterial infusion, 69.2% of the total activity was located in the liver, 3.6% in the spleen, 3.2% in the lungs, and 3.5% in the general circulation. Following venous injection, 50.7% of the radioactivity was found in the liver, 9.1% in the spleen, 8.6% in the lungs, and 6.7% in the peripheral blood. Once the liposomes entered the systemic circulation, they were cleared at the same rate (half-life beta = 21.5 hours) independent of their route of administration. Increased hepatic liposome uptake should translate into higher local and lower systemic liposomal drug levels.
为了提高脂质体用于药物递送时的肝脏摄取率，通过选择性动脉灌注给予空泡囊。将带负电荷的多层脂质体用锝-99m标记后注入健康成年犬体内。每只犬以2 mL/分钟的速度在10分钟内接受100 mg/m²的脂质。脂质体通过胃十二指肠动脉近端闭塞后经肝总动脉、经肠系膜前动脉以及经头静脉给药。通过计算机辅助外部成像技术确定分布情况（肝脏、脾脏和肺）。平均而言，动脉灌注后，总活性的69.2%位于肝脏，3.6%位于脾脏，3.2%位于肺，3.5%位于体循环。静脉注射后，50.7%的放射性出现在肝脏，9.1%在脾脏，8.6%在肺，6.7%在外周血。一旦脂质体进入体循环，它们以相同的速率（β半衰期 = 21.5小时）被清除，与给药途径无关。肝脏脂质体摄取率的提高应转化为更高的局部脂质体药物水平和更低的全身脂质体药物水平。
