TY - JOUR
T1 - Distribution and pharmacology of intravenous 99mTc-labeled multilamellar liposomes in rats and mice
AU - Kasi, Leela P.
AU - Lopez-Berestein, Gabriel
AU - Mehta, Kapil
AU - Rosenblum, Michael
AU - Glenn, Howard J.
AU - Haynie, Thomas P.
AU - Mavligit, Giora
AU - Hersh, Evan M.
N1 - Funding Information:
The reticuloendothelial system is a logical target for the selective delivery of macrophage activators. The mechanism by which macrophages take up liposomes is through phagocytosis. In these studies we have used multilamellar vesicles consisting of phosphatidylserine and phosphatidylcholine in the molar ratio 3:7. We observed that these vesicles were mainly taken up by the liver and spleen, and that by increasing the dose of the lipid there was enhanced uptake by the lung and kidney. In addition, at doses of 500 mg/kg, there was demonstrable uptake by the macrophages obtained by pulmonary lavage when compared with uptake when lower doses were injected. We observed that at 24 h after injection, 70% of the labeled liposomes were retained whereas no retention was found when the free isotope was used. The results of the pharmacological studies indicate that the liposomes may serve as a sustained release system for drugs and that the encapsulation enhances the distribution of the label to tissue compartments. These data indicate that liposomes may be a useful tool for delivering drugs to the RES and that the increased delivery to lung accomplished by increasing the dose makes this approach attractive for treatment of organs most frequently affected by metastatic diseases as lung and liver. Acknowledgements-This work was supported in part by NIH Grant 551 I. The authors wish to express their gratitude to Marvin Gunz and Irene Teckemeyer for their technical assistance and to MS Lois Butterwick for the preparation of this manuscript.
PY - 1984
Y1 - 1984
N2 - The use of liposomes for the delivery of macrophage activators offers a new approach for the selective targeting of antitumor therapy. We have investigated the distribution, retention, and pharmacology of multilamellar liposomes (phosphatidylserine (PS): phosphatidylcholine (PC) 3:7) on i.v. injection in normal rats. Sprague-Dawley rats were injected with doses varying from 300 to 1000 mg/kg of 99mTc-liposomes. The organ distribution of doses ranging from 300 to 500 mg/kg showed 45% mean uptake by liver, 25% by spleen, and 4% by lung. At higher doses of 800-1000 mg/kg, uptake in the lung increased significantly to 9 ± 3%. Whole body retention at 24 h after i.v. injection in Hale Stoner mice was 70%. The blood disappearance curve was biphasic and compared with the free isotope, a decrease was observed in the initial a phase t 1 2 while the terminal phase t 1 2 increased by 100%. These data suggest that encapsulation prolongs the initial distribution to the peripheral compartments and that higher doses may increase uptake by organs other than the liver.
AB - The use of liposomes for the delivery of macrophage activators offers a new approach for the selective targeting of antitumor therapy. We have investigated the distribution, retention, and pharmacology of multilamellar liposomes (phosphatidylserine (PS): phosphatidylcholine (PC) 3:7) on i.v. injection in normal rats. Sprague-Dawley rats were injected with doses varying from 300 to 1000 mg/kg of 99mTc-liposomes. The organ distribution of doses ranging from 300 to 500 mg/kg showed 45% mean uptake by liver, 25% by spleen, and 4% by lung. At higher doses of 800-1000 mg/kg, uptake in the lung increased significantly to 9 ± 3%. Whole body retention at 24 h after i.v. injection in Hale Stoner mice was 70%. The blood disappearance curve was biphasic and compared with the free isotope, a decrease was observed in the initial a phase t 1 2 while the terminal phase t 1 2 increased by 100%. These data suggest that encapsulation prolongs the initial distribution to the peripheral compartments and that higher doses may increase uptake by organs other than the liver.
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U2 - 10.1016/0047-0740(84)90028-7
DO - 10.1016/0047-0740(84)90028-7
M3 - Article
C2 - 6735607
AN - SCOPUS:0021271439
VL - 11
SP - 35
EP - 37
JO - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
JF - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
SN - 0969-8051
IS - 1
ER -