Gibaud S, Andreux J P, Weingarten C, Renard M, Couvreur P
Laboratoire de Pharmacie Galénique, U.R.A. CNRS 1218, France.
Eur J Cancer. 1994;30A(6):820-6. doi: 10.1016/0959-8049(94)90299-2.
The in vivo myelosuppressive effects of free and polyalkylcyanoacrylate-bound doxorubicin were compared in a mouse model. After intravenous administration of 11 mg/kg body weight of doxorubicin either free or bound to polyisobutyl (doxo-PIBCA) or polyisohexylcyanoacrylate (doxo-PIHCA) nanoparticles, we studied the total and differential counts of blood, bone marrow and spleen cells; the number of granulocyte progenitors (CFU-GM) was determined by culture. Doxorubicin concentrations were measured with an HPLC method in the bone marrow and the spleen. Doxo-PIHCA nanoparticles showed the highest and longest myelosuppressive effects which correlated well with a high concentration of the drug in the bone marrow and the spleen. Moreover, it was found that PIHCA nanoparticles induced the release of colony stimulating factors, which might account for the observed increase of toxic effects of doxorubicin on bone marrow progenitors. These data also indicate that a more precise evaluation of the myelosuppressive effects of targeted formulations of anticancer drugs is needed, which may be attained by studies on bone marrow progenitors.
在小鼠模型中比较了游离阿霉素和聚烷基氰基丙烯酸酯结合的阿霉素的体内骨髓抑制作用。静脉注射11mg/kg体重的游离阿霉素或与聚异丁基（阿霉素 - PIBCA）或聚异己基氰基丙烯酸酯（阿霉素 - PIHCA）纳米颗粒结合的阿霉素后，我们研究了血液、骨髓和脾细胞的总数及分类计数；通过培养确定粒细胞祖细胞（CFU - GM）的数量。采用高效液相色谱法测定骨髓和脾中的阿霉素浓度。阿霉素 - PIHCA纳米颗粒显示出最高且持续时间最长的骨髓抑制作用，这与骨髓和脾中高浓度的药物密切相关。此外，发现PIHCA纳米颗粒可诱导集落刺激因子的释放，这可能解释了观察到的阿霉素对骨髓祖细胞毒性作用增加的原因。这些数据还表明，需要更精确地评估抗癌药物靶向制剂的骨髓抑制作用，这可通过对骨髓祖细胞的研究来实现。
