Selective in vivo localization of daunorubicin small unilamellar vesicles in solid tumors.

Abstract

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.