Selective in vivo localization of daunorubicin small unilamellar vesicles in solid tumors.
Small unilamellar vesicles (SUVs), consisting of highly purified distearoyl phosphatidylcholine and cholesterol (2:1 mol ratio) selectively increased the delivery of entrapped daunorubicin to solid tumors in vivo. When measured against free drug, SUV-entrapped daunorubicin produced a nearly 10-fold increase in tumor uptake and efficacy when used to treat a murine lymphosarcoma model (P-1798). In a second murine solid tumor model, MA16C mammary adenocarcinoma, the median survival time for daunorubicin SUV treatment at 2 mg/kg (72 days) was equivalent to the median survival time for the free drug optimal dose, 20 mg/kg (70 days), again indicating a 10-fold increased therapeutic efficacy. When compared at maximum efficacious doses in the MA16C model, the proportion of long-term survivors was greater with daunorubicin SUVs: 10 long-term survivors of 10 mice treated with daunorubicin SUVs at 25 mg/kg versus 4 long-term survivors of 10 mice treated with free drug at 20 mg/kg. The lowest toxic doses for MA16C tumor-bearing animals (treatment median survival times less than controls) were 25 mg/kg for free drug and 40 mg/kg for daunorubicin SUVs. The demonstration of enhanced antineoplastic activity and an increased tolerance for daunorubicin suggests that this specific SUV composition may be an effective delivery system for a wide range of chemotherapeutic agents in the treatment of solid tumors.
Forssen
E A
EA
Vestar, Inc., San Dimas, California 91773.
Coulter
D M
DM
Proffitt
R T
RT
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001682:Biological Availability; D003630:Daunorubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004337:Drug Carriers; D008081:Liposomes; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D003630:Daunorubicin