Construction and characterization of adriamycin-loaded canine red blood cells as a potential slow delivery system.
Adriamycin was internalized in canine red blood cells (RBC) by two procedures involving (a) simple diffusion of the drug into cells and (b) hypotonic dialysis followed by isotonic resealing. The two procedures yielded comparable amounts of encapsulated adriamycin, around 35 micrograms/10(9) RBC. Exposure of adriamycin-loaded RBC to 0.16% glutaraldehyde consistently slowed down the rate of efflux of the drug as compared with non-glutaraldehyde-treated cells: after 1 h of incubation at 37 degrees C, greater than 80% of adriamycin was still present inside the glutaraldehyde-treated RBC, while at 24 h it was 66%, compared to 10% and 1%, respectively, in the adriamycin-loaded, non-glutaraldehyde-treated cells. Canine RBC showed a higher rate of transformation of adriamycin than the human cells, the only intracellular metabolite being adriamycinol, which is apparently formed by the NADPH-dependent enzyme aldehyde reductase. Production of adriamycinol was remarkably lower in the glutaraldehyde-treated RBC, as a result of progressive and extensive inactivation of hexose monophosphate shunt activity responsible for NADPH formation. These results, coupled with the known selective targeting of glutaraldehyde-treated RBC to liver, hold promise as to in vivo applications of this drug delivery system in antineoplastic therapy.
Tonetti
M
M
Veterinary Toxicology, USDA-ARS, College Station, Texas 77840.
Astroff
B
B
Satterfield
W
W
De Flora
A
A
Benatti
U
U
DeLoach
J R
JR
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage* / Q000097:blood; D004337:Drug Carriers; D004910:Erythrocyte Membrane; D004912:Erythrocytes / Q000378:metabolism; D005976:Glutaral; D006600:Hexosephosphates / Q000097:blood; D066298:In Vitro Techniques; D009996:Osmotic Fragility / Q000187:drug effects
D004337:Drug Carriers; D006600:Hexosephosphates; D004317:Doxorubicin; D005976:Glutaral