Intraneoplastic application of metrizamide-containing liposomes: kinetic studies with computed tomography.
Liposomes may serve as drug carriers not only for systemic chemotherapy but also for intraneoplastic drug therapy because they show a sustained drug release. In the present study, the in vivo kinetics of intraneoplastic deposits of large multilamellar vesicles containing metrizamide was followed up in a rat tumor model with computed tomography. The influence of four different lipid compositions on the retardation capacity of large multilamellar liposomes was investigated. By comparing the dynamic data of X-ray attenuation and volume of liposome deposits, a rank order for the in vivo stability of metrizamide containing multilamellar vesicles could be established: the least stable liposomes were made of pure dimyristoyl-phosphatidyl-choline, the most stable type was made of equimolar parts of stearoyl-palmitoyl-phosphatidyl-choline and cholesterol. Of intermediate stability were liposomes made of equimolar parts of dimyristoyl-phosphatidyl-choline and cholesterol, and those made of pure stearoyl-palmitoyl-phosphatidyl-choline. The addition of 50% cholesterol increased the membrane stability of both dimyristoyl-phosphatidyl-choline and stearoyl-palmitoyl-phosphatidyl-choline liposomes. No diffusion of large multilamellar liposomes away from the injection site was observed. The in vivo stability of the liposomes was considerably less than that observed in vitro, suggesting active degradation processes. It is concluded that large, multilamellar liposomes may be suitable carriers for intraneoplastic chemotherapy. The present model is easily adaptable to be transferred into clinical conditions, and may allow direct monitoring of intraneoplastic liposome-mediated chemotherapy in human brain tumors.
Wowra
B
B
Department of Neurosurgery, University of Heidelberg, Germany.
Cremer
K
K
Stricker
H
H
Zeller
W J
WJ
D000818:Animals; D001415:Back; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine; D004337:Drug Carriers; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy; D007279:Injections, Subcutaneous; D008081:Liposomes; D008297:Male; D008793:Metrizamide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D010713:Phosphatidylcholines; D051381:Rats; D011919:Rats, Inbred Strains; D015203:Reproducibility of Results; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol; D008793:Metrizamide; D004134:Dimyristoylphosphatidylcholine