In vivo liver and lung targeting of adriamycin encapsulated in glutaraldehyde-treated murine erythrocytes.
Treatment of adriamycin-loaded erythrocytes from B6D2F1 mice with 0.1% glutaraldehyde produced the following effects: a considerable decrease in the in vitro leakage of the unmodified drug and a selective liver (and, to a lesser extent, lung) uptake of the encapsulated drug (70% of the injected dose) compared to drug leakage from, and tissue distribution of, carrier erythrocytes not treated with glutaraldehyde. The liver vascular bed was not saturated by five daily intravenous injections of 20 microliters of glutaraldehyde-treated erythrocytes, which allows a total dosage of 200 micrograms of the drug (half the LD50 value) to be administered. No appreciable liver damage results from extensive and prolonged uptake of glutaraldehyde-treated carrier erythrocytes. Entrapment of adriamycin within erythrocytes along with glutaraldehyde treatment of the carrier cells seems to be a promising therapeutic strategy against liver (and lung) tumors.
Zocchi
E
E
Institute of Biochemistry, University of Genoa, Italy.
Tonetti
M
M
Polvani
C
C
Guida
L
L
Benatti
U
U
De Flora
A
A
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004912:Erythrocytes; D005260:Female; D005976:Glutaral / Q000494:pharmacology; D006403:Hematologic Tests; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D014018:Tissue Distribution
D004337:Drug Carriers; D004317:Doxorubicin; D005976:Glutaral