Batrakova E V, Dorodnych T Y, Klinskii E Y, Kliushnenkova E N, Shemchukova O B, Goncharova O N, Arjakov S A, Alakhov V Y, Kabanov A V
Moscow Institute of Biotechnology, Inc., and Russian Research Center of Molecular Diagnostics and Therapy.
Br J Cancer. 1996 Nov;74(10):1545-52. doi: 10.1038/bjc.1996.587.
The chemosensitising effects of poly(ethylene oxide)-poly(propylene oxide)-poly-(ethylene oxide) (PEO-PPO-PEO) block copolymers (Pluronic) in multidrug-resistant cancer cells has been described recently (Alakhov VY, Moskaleva EY, Batrakova EV, Kabanov AV 1996, Biocon. Chem., 7, 209). This paper presents initial studies on in vivo evaluation of Pluronic copolymers in the treatment of cancer. The anti-tumour activity of epirubicin (EPI) and doxorubicin (DOX), solubilised in micelles of Pluronic L61, P85 and F108, was investigated using murine leukaemia P388 and daunorubicin-sensitive Sp2/0 and -resistant Sp2/0(DNR) myeloma cells grown subcutaneously (s.c.). The study revealed that the lifespan of the animals and inhibition of tumour growth were considerably increased in mice treated with drug/copolymer compositions compared with animals treated with the free drugs. The anti-tumour activity of the drug/copolymer compositions depends on the concentration of the copolymer and its hydrophobicity, as determined by the ratio of the lengths of hydrophilic PEO and hydrophobic PPO segments. The data suggest that higher activity is associated with more hydrophobic copolymers. In particular, a significant increase in lifespan (T/C> 150%) and tumour growth inhibition (> 90%) was observed in animals with Sp2/0 tumours with EPI/P85 and DOX/L61 compositions. The effective doses of these compositions caused inhibition of Sp2/0 tumour growth and complete disappearance of tumour in 33-50% of animals. Future studies will focus on the evaluation of the activity of Pluronic-based compositions against human drug-resistant tumours.
聚环氧乙烷-聚环氧丙烷-聚环氧乙烷（PEO-PPO-PEO）嵌段共聚物（普朗尼克）在多药耐药癌细胞中的化学增敏作用最近已有报道（Alakhov VY，Moskaleva EY，Batrakova EV，Kabanov AV 1996，Biocon. Chem.，7，209）。本文介绍了普朗尼克共聚物治疗癌症的体内评价初步研究。使用皮下生长的小鼠白血病P388以及对柔红霉素敏感的Sp2/0和耐药的Sp2/0（DNR）骨髓瘤细胞，研究了溶解于普朗尼克L61、P85和F108胶束中的表柔比星（EPI）和多柔比星（DOX）的抗肿瘤活性。研究表明，与接受游离药物治疗的动物相比，接受药物/共聚物组合物治疗的小鼠的寿命和肿瘤生长抑制显著增加。药物/共聚物组合物的抗肿瘤活性取决于共聚物的浓度及其疏水性，疏水性由亲水性PEO段和疏水性PPO段的长度比决定。数据表明，更高的活性与疏水性更强的共聚物有关。特别是，在患有Sp2/0肿瘤的动物中，观察到使用EPI/P85和DOX/L61组合物时寿命显著增加（T/C>150%）且肿瘤生长抑制（>90%）。这些组合物的有效剂量导致33%-50%的动物中Sp2/0肿瘤生长受到抑制且肿瘤完全消失。未来的研究将集中于评估基于普朗尼克的组合物对人类耐药肿瘤的活性。
