title: Distribution of [3H]cholesterol-labelled liposomes with or without praziquantel in mice infected with Mesocestoides corti (Cestoda) tetrathyridia.
abstract: The anthelmintic drug praziquantel (PZQ) has a short half-life in the circulation, necessitating repeated daily administration of PZQ for the therapy of larval stages of cestodes. The effect of incorporation of PZQ into multilamellar liposomes on their biodistribution in Mesocestoides corti (syn. M. vogae) infected mice has been examined using [3H]cholesterol as a liposomal marker. Incorporation of PZQ significantly increased the average size of liposomes with 70.3% of [3H]lip.PZQ particles up to 1.9 microm, whereas higher portion of [3H]liposomes (66.3% of total) were of smaller (up to 1.3 microm). Both liposome preparations were given intraperitoneally to avoid rapid sequestration in the liver. There were significant differences between [3H]liposomes and [3H]lip.PZQ-associated radioactivity in peritoneal adherent cells, liver- and peritoneal larvae, liver, spleen and lymph nodes within 16 days of examination. The highest uptake (about 2-fold more [3H]lip.PZQ than [3H]liposomes from the total dose) was found in peritoneal cells on day 1 post therapy (p.t.) followed by a rapid decline. The kinetic of decline in these cells recovered on day 1 p.t. was studied also in vitro. Disappearance of the marker due to the breakdown of liposomes and efflux of lipids and PZQ from cells was slower for [3H]lip.PZQ in comparison with drug-free liposomes and was not completed after 4 days-incubation. Significantly increased levels of radioactivity, more in [3H]liposomes treated groups, were recorded in the liver- and peritoneal larvae between days 8-16 p.t. indicating re-utilization of cholesterol by the larvae. The data suggest that incorporation of PZQ into liposomes contributes to the enlargement of liposome average size and slows down their degradation in phagocytosing cells. In this respect, these cells could serve as the secondary circulating depots for PZQ releasing it slowly to the circulation.
authors.affiliation: Parasitological Institute, The Slovak Academy of Sciences, Kosice, Slovak Republic. hrcka@saske.sk
authors.forename: G
authors.initials: G
authors.lastname: Hrckova
authors.forename: S
authors.initials: S
authors.lastname: Velebny
authors.forename: M
authors.initials: M
authors.lastname: Giboda
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage*; D002590:Cestode Infections / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000493:pharmacokinetics*; D004337:Drug Carriers; D008081:Liposomes / Q000493:pharmacokinetics*; D008297:Male; D008645:Mesocestoides; D051379:Mice; D008813:Mice, Inbred ICR; D010537:Peritoneum / Q000378:metabolism; D011223:Praziquantel / Q000008:administration & dosage*; D014018:Tissue Distribution
chemical_list: D000871:Anthelmintics; D004337:Drug Carriers; D008081:Liposomes; D011223:Praziquantel; D002784:Cholesterol