Trapping of chemical carcinogens with magnetic polyethyleneimine microcapsules: III. In vivo trapping of electrophiles from N-methyl-N-nitrosourea and recovery from feces.
The use of semipermeable magnetic polyethyleneimine (PEI) microcapsules for trapping carcinogens in vivo is described. After intragastric administration to rodents, up to 40% of the microcapsules were extracted magnetically from fecal suspensions, with most recovered in the first 24 h after administration. The mean diameter of the recovered microcapsule population was in some cases larger than that administered. The changes in size distribution and incomplete recovery could be ascribed to the magnetic extraction technique rather than loss or destruction of microcapsules in vivo. By contrast, magnetic hemoglobin microcapsules were not stable in vivo and were recovered in very low yields. An important factor determining the recovery of administered PEI microcapsules was the amount of encapsulated magnetite. Microcapsules administered intragastrically to rodents trapped up to 0.02% of an intragastric dose of N-[methyl-14C]-N-nitrosourea (1). Binding was dose dependent with the limiting factor being the number of available binding sites; increasing the number of administered microcapsules accordingly increased the total amount of 1 bound by them. After administration of [14C--CH3]-derivatized microcapsules, the recovery from feces of microcapsule-associated radioactivity was 48-74%, up to twice the numerical recovery. Although this indicates that microencapsulated labeled core PEI was recovered, it could not be released upon sonication. This was due in part to an increased resistance of the microcapsules to sonication caused by GI tract transit that was probably due to nonspecific absorption of substances. Subsequent acid treatment released some radiolabeled core PEI, as indicated by precipitation with polyacrylic acid. Excreted microcapsules were found to have material adsorbed both on the outer membrane surface and also throughout the membrane.
D000818:Animals; D002214:Capsules; D003959:Diamines; D005243:Feces / Q000032:analysis; D052203:Ferrosoferric Oxide; D007501:Iron; D008280:Magnetics; D008297:Male; D008770:Methylnitrosourea / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D010087:Oxides; D011094:Polyethyleneimine / Q000032:analysis; D011095:Polyethylenes / Q000032:analysis; D051381:Rats
D002214:Capsules; D003959:Diamines; D010087:Oxides; D011095:Polyethylenes; D008770:Methylnitrosourea; D011094:Polyethyleneimine; D007501:Iron; D052203:Ferrosoferric Oxide; C007297:1,6-diaminohexane