TUMOR UPTAKE OF DOXORUBICIN IN POLYETHYLENE GLYCOL-COATED LIPOSOMES AND THERAPEUTIC EFFECT AGAINST A XENOGRAFTED HUMAN PANCREATIC-CARCINOMA

This study tested the therapeutic efficacy of doxorubicin hydrochlorid e in two formulations: free in saline suspension and encapsulated in p olyethylene glycol-coated, long-circulating liposomes. The drug formul ations at a dose level of 3 mg doxorubicin per kg body weight were inj ected intravenously to treat the human pancreatic carcinoma AsPC-1, im planted s.c. into nude Swiss mice. Liposome-encapsulated doxorubicin w as significantly more effective in inhibiting tumour growth and in eff ecting cures, and had only minor systemic toxic side-effects, indicate d by a transient weight loss. Confocal laser scanning microscopy was u sed to determine the tumour uptake and the clearance of doxorubicin in the free and in the liposomal forms. The liposome-encapsulated doxoru bicin entered the tumour in greater quantity, and remained in the tumo ur longer, than the free drug. The liposome formulation produced a six fold or greater increase in doxorubicin at the disease site. It is pro bable that increased penetration into the tumour, and long presence wi th slow drug release from liposomes in the tumour, account for the enh anced therapeutic effect when the drug was encapsulated in polyethylen e glycol-coated liposomes.