Kunieda K, Seki T, Nakatani S, Wakabayashi M, Shiro T, Inoue K, Sougawa M, Kimura R, Harada K
Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Br J Cancer. 1993 Apr;67(4):668-73. doi: 10.1038/bjc.1993.124.
We performed an experimental study on slow releasing anticancer drug implantation treatment as a new therapy for hepatocellular carcinoma. Hydroxyapatite (HAP) was chosen for the carrier material and doxorubicin hydrochloride (DOX) for anticancer agent. DOX-HAP was produced by adsorbing DOX to porous HAP particles of 1375 +/- 125 microns diameter using the freeze drying method. In vitro experiments showed slow release of the drug resulting in the steady release of DOX from HAP for 1 month duration. In healthy white rabbits with DOX-HAP implantation in the liver, serum DOX was not detectable, and DOX release rate was stable at the implanted region after 7, 14, and 21 days. When DOX-HAP (DOX; 100 mg kg-1) was administered to mice with sarcoma 180, an improved survival rate was observed without acute toxicity. We also found that VX2 liver tumour growth on white rabbit was inhibited by implantation of DOX-HAP, without acute toxicity. We hope that DOX-HAP implantation therapy will open up new avenues for the treatment of hepatoma.
我们开展了一项关于缓释抗癌药物植入治疗的实验研究,将其作为肝细胞癌的一种新疗法。选择羟基磷灰石(HAP)作为载体材料,盐酸阿霉素(DOX)作为抗癌剂。采用冷冻干燥法将DOX吸附到直径为1375±125微米的多孔HAP颗粒上,制备出DOX-HAP。体外实验表明药物缓慢释放,DOX从HAP中持续稳定释放达1个月。在肝脏植入DOX-HAP的健康白兔中,血清中检测不到DOX,且在7天、14天和21天后植入区域的DOX释放率稳定。当给患有肉瘤180的小鼠施用DOX-HAP(DOX;100毫克/千克)时,观察到存活率提高且无急性毒性。我们还发现,在白兔中植入DOX-HAP可抑制VX2肝肿瘤生长,且无急性毒性。我们希望DOX-HAP植入疗法将为肝癌治疗开辟新途径。