Enhanced antitumor activity of adriamycin by encapsulation in mouse erythrocytes targeted to liver and lungs.
Adriamycin was encapsulated within human and murine (B6D2F1 female mice) erythrocytes using a procedure based on hypotonic hemolysis followed by isotonic resealing and reannealing. Following drug encapsulation the murine erythrocytes were treated with glutaraldehyde to obtain: a) control of Adriamycin efflux from loaded erythrocytes, b) appropriate hepatic and pulmonary targeting of the in vivo re-infused cells. The antitumor effect of equivalent amounts of bolus (i.v.) administered Adriamycin, 1) free, 2) encapsulated within erythrocytes, 3) encapsulated within glutaraldehyde-treated erythrocytes, was compared using an in vivo model of metastasis based on selective hepatic and pulmonary dissemination of intrasplenically injected L1210 cells in B6D2F1 mice. The therapeutic index (TI) of Adriamycin encapsulated within glutaraldehyde-treated erythrocytes increased by more than two-fold over that of the free drug.
Benatti
U
U
Institute of Biochemiostry, University of Genoa, Italy.
Zocchi
E
E
Tonetti
M
M
Guida
L
L
Polvani
C
C
De Flora
A
A
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D004912:Erythrocytes; D005260:Female; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation
D004337:Drug Carriers; D004317:Doxorubicin