In vivo biodistribution of erythrocytes and polyethyleneglycol-phosphatidylethanolamine micelles carrying the antitumour agent dequalinium.
Dequalinium (DQA), a lipophilic drug with anti-cancer activity has been incorporated into mouse red blood cells (DQA-RBCs) and polyethylene glycol phosphatidylethanolamine micelles (DQA-PEG-PE-micelles) in order to overcome the drug's solubility problems and to make it suitable for in vivo applications. The incorporation of DQA into erythrocytes, the release of DQA from RBCs in the presence of autologous plasma and the biodistribution of 51Cr-DQA-RBCs and 111In-DQA-PEG-PE micelles in mice has been studied. Under optimal conditions, up to 84.9% of 0.2 mM dequalinium can be incorporated into erythrocytes. The incubation of DQA-RBC with serum leads to the release of DQA over a period of 24 h. Since 51Cr-DQA-RBCs were found to have a long circulation half-life (5-6 days), the use of RBCs as a sustained release system for DQA can be suggested. In contrast to DQA containing erythrocytes, however, DQA loaded 111In-PEG-PE micelles displayed a shorter half-life (4 h) due to their quick uptake by the liver. The further exploration of PEG-PE micelles as a fast acting release system for DQA appears warranted.
Lizano
Carmen
C
Departmento de Bioquímica y Biología Molecular, Universidad de Alcalá, Madrid, Spain.
Weissig
Volkmar
V
Torchilin
Vladimir P
VP
Sancho
Pilar
P
García-Pérez
Ana Isabel
AI
Pinilla
Montserrat
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D003868:Dequalinium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004912:Erythrocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008823:Micelles; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D008823:Micelles; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D003868:Dequalinium