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 doxorubici n in two formulations: free in saline suspension and encapsulated in s terically stabilized liposomes composed of hydrogenated soy phosphatid ylcholine/2cholesterol/polyethylene glycol-distearoyl-phosphatidyl-eth anolamine (Doxil, Liposome Technology, Inc., Menlo Park, CA). Method. The drug formulations were injected intravenously to treat human prost ate carcinoma PC-3, implanted subcutaneously into nude Swiss mice. Con focal laser scan microscopy and microfluorometry were used to determin e tissue distribution and to quantitate drug uptake. Results. Laser sc an microscope and microfluorometer studies showed that the liposome-en capsulated drug entered the liver, the kidneys, and the tumor in great er quantity and remained in the liver and in the tumor longer than the free drug. The liposome formulation produced a 25-fold increase in do xorubicin 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 cur rent study demonstrated the therapeutic efficacy of doxorubicin, encap sulated 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 pro bably accounted for the enhanced therapeutic effect of doxorubicin in sterically stabilized liposomes.