In vitro release and depot effect after intratumoral application of metrizamide-containing liposomes.
The drug release and intratumoral residence time of small and large liposomes composed of saturated phospholipids and cholesterol were measured in vitro and in tumor-bearing rats by computed tomography. The in vitro release of metrizamide at 37 degrees C was higher in tissue fluid than in diluted serum and PBS-buffer. The extent of release was 20%/48 h for the 100 nm-liposomes and 10%/48 h for the 480 nm liposomes. The decrease of x-ray contrast after intratumoral application resulted in a half-life of t50 = 0.05 d for metrizamide solution and t50 = 0.42 d for small liposomes. Large liposomes showed a linear decrease in contrast, the half-life being t50 = 15 d. While small liposomes rapidly leave the tumor, large liposomes rest intact in the tumor for about 30 d. Therefore they fulfill a fundamental prerequisite for intratumoral depots of cytostatics with controlled release.
Mentrup
E
E
Institute of Pharmaceutical Technology and Biopharmaceutics University, Heidelberg, Fed. Rep. of Germany.
Wowra
B
B
Zeller
W J
WJ
Sturm
V
V
Stricker
H
H
D000818:Animals; D003692:Delayed-Action Preparations; D007267:Injections; D008081:Liposomes; D008297:Male; D008793:Metrizamide / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010316:Particle Size; D051381:Rats
D003692:Delayed-Action Preparations; D008081:Liposomes; D008793:Metrizamide