Rhodanese and sodium thiosulfate encapsulated in mouse carrier erythrocytes. II. In vivo survivability and alterations in physiologic and morphologic characteristics.
Biodegradable drug carrier mechanisms were employed in drug antagonism studies. Prior studies indicated that erythrocytes containing encapsulated rhodanese and sodium thiosulfate metabolized cyanide to thiocyanate in vitro. Studies were conducted to investigate the properties of these sulfurtransferase-loaded red blood cells in vivo by administering the carrier red blood cells intravenously. Approximately 40 to 50% of the cells were eliminated within the first few hours while the remaining loaded erythrocytes persisted in the circulation. The present studies were initiated to investigate the characteristics of the disposition of the loaded erythrocytes and to examine differences in the properties between carrier and noncarrier erythrocytes. Also, the disposition and viability of the erythrocytes in vivo were studied with relation to various biochemical, physiological, and morphological properties. These studies indicated that the carrier erythrocytes had a smaller cell volume and were more susceptible to hemolysis than normal erythrocytes. Morphologic studies by electron microscopy indicated that extensive morphologic changes occurred during the procedures after hypotonic dialysis, isotonicity adjustment, and resealing were completed. Differences were noted between those cells that were only resealed and those cells that were also subjected to annealing. The morphologic characteristics of most of the cells were restored to the "normal" morphologic appearance only after annealing. Annealed erythrocytes' in vivo survivability was correlated with the physical properties of these cells.
Leung
P
P
Department of Medical Pharmacology and Toxicology, Texas A & M University, College of Medicine, College Station 77843-1114.
Davis
R W
RW
Yao
C C
CC
Cannon
E P
EP
Way
J L
JL
D000818:Animals; D002214:Capsules; D004337:Drug Carriers; D004912:Erythrocytes / Q000648:ultrastructure; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009996:Osmotic Fragility; D013884:Thiosulfate Sulfurtransferase / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013885:Thiosulfates / Q000008:administration & dosage* / Q000493:pharmacokinetics
D002214:Capsules; D004337:Drug Carriers; D013885:Thiosulfates; D013884:Thiosulfate Sulfurtransferase; C017717:sodium thiosulfate