ANTHRACYCLINE ANTIBIOTICS NONCOVALENTLY INCORPORATED INTO THE BLOCK-COPOLYMER MICELLES - IN-VIVO EVALUATION OF ANTICANCER ACTIVITY

The chemosensitising effects of poly(ethylene oxide)-poly(propylene ox ide)-poly-(ethylene oxide) (PEO-PPO-PEO) block copolymers (pluronic) i n multidrug-resistant cancer cells has been described recently (Alakho v VY, Moskaleva EY, Batrakova EV, Kabanov AV 1996, Biocon. Chem., 7, 2 09). This paper presents initial studies on in vivo evaluation of Plur onic copolymers in the treatment of cancer. The anti-tumour activity o f epirubicin (EPI) and doxorubicin (DOX), solubilised in micelles of P luronic L61, P85 and F108, was investigated using murine leukaemia P38 8 and daunorubicin-sensitive Sp2/0 and -resistant Sp2/0(DNR) myeloma c ells grown subcutaneously (s.c.). The study revealed that the lifespan of the animals and inhibition of tumour growth were considerably incr eased in mice treated with drug/copolymer compositions compared with a nimals treated with the free drugs. The anti-tumour activity of the dr ug/copolymer compositions depends on the concentration of the copolyme r and its hydrophobicity, as determined by the ratio of the lengths of hydrophilic PEO and hydrophobic PPO segments. The data suggest that h igher activity is associated with more hydrophobic copolymers. In part icular, a significant increase in lifespan (T/C>150%) and tumour growt h inhibition (>90%) was observed in animals with Sp2/0 tumours with EP I/P85 and DOX/L61 compositions. The effective doses of these compositi ons caused inhibition of Sp2/0 tumour growth and complete disappearanc e of tumour in 33-50% of animals. Future studies will focus on the eva luation of the activity of Pluronic-based compositions against human d rug-resistant tumours.