Liposome distribution after intravenous and selective intraarterial infusion in dogs.
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.
Wright
K C
KC
Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Kasi
L P
LP
Jahns
M S
MS
Hashimoto
S
S
Wallace
S
S
D000818:Animals; D004285:Dogs; D004337:Drug Carriers; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008081:Liposomes / Q000493:pharmacokinetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008168:Lung / Q000000981:diagnostic imaging; D008638:Mesenteric Arteries; D011877:Radionuclide Imaging; D013154:Spleen / Q000000981:diagnostic imaging; D013667:Technetium; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D013667:Technetium