J. Vaage et al., TUMOR UPTAKE OF DOXORUBICIN IN POLYETHYLENE GLYCOL-COATED LIPOSOMES AND THERAPEUTIC EFFECT AGAINST A XENOGRAFTED HUMAN PANCREATIC-CARCINOMA, British Journal of Cancer, 75(4), 1997, pp. 482-486
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.