Tissue distribution and therapeutic effect of intravenous free or encapsulated liposomal doxorubicin on human prostate carcinoma xenografts.
BACKGROUND
The authors compared the therapeutic effects of doxorubicin in two formulations: free in saline suspension and encapsulated in sterically stabilized liposomes composed of hydrogenated soy phosphatidylcholine/2cholesterol/polyethylene glycol-distearoyl-phosphatidyl-ethanolamine (Doxil, Liposome Technology, Inc., Menlo Park, CA).


METHODS
The drug formulations were injected intravenously to treat human prostate carcinoma PC-3, implanted subcutaneously into nude Swiss mice. Confocal laser scan microscopy and microfluorometry were used to determine tissue distribution and to quantitate drug uptake.


RESULTS
Laser scan microscope and microfluorometer studies showed that the liposome-encapsulated drug entered the liver, the kidneys, and the tumor in greater quantity and remained in the liver and in the tumor longer than the free drug. The liposome formulation produced a 25-fold increase in doxorubicin at the disease site. Doxil was significantly more effective than the free drug in inhibiting growth and in effecting cures and had only minor and temporary systemic toxic effects.


CONCLUSIONS
The current study demonstrated the therapeutic efficacy of doxorubicin, encapsulated in sterically stabilized liposomes, against prostate carcinoma. Decreased systemic elimination, increased penetration into the tumor, and long liposome presence with slow drug release into the tumor probably accounted for the enhanced therapeutic effect of doxorubicin in sterically stabilized liposomes.
Vaage
J
J
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Barberá-Guillem
E
E
Abra
R
R
Huang
A
A
Working
P
P
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014183:Transplantation, Heterologous
D008081:Liposomes; D004317:Doxorubicin