电渗辅助泵直接瘤内给药盐酸阿霉素的有用性

Ayu Ito, S. Itakura, Yuya Hasegawa, Miyu Hashimoto, Akie Okada, Mamoru Hirafuji, H. Nakamura, K. Sugibayashi, H. Todo
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引用次数: 1

摘要

通过静脉注射(i.v.)或口服抗癌药物接受化疗的患者经常会出现副作用。在本研究中,电渗流(EO)泵用于直接给药副作用最小的抗癌药物。使用盐酸阿霉素(DXR)作为抗癌药物,并与静脉给药进行比较,评价其抗肿瘤作用和毒性。Balb/c雌性小鼠皮下移植稳定表达荧光素酶的癌症细胞系(4T1/Luc),并使用EO泵或使用注射器以慢速(0.6µL/min)在肿瘤内(i.t.)施用20μL DXR溶液(1.0 mg/mL)。相比之下,100μL DXR溶液以相同剂量和5倍高的剂量通过尾静脉注射。使用EO泵直接i.t.给药DXR观察到肿瘤生长抑制作用而没有显著的体重减轻。另一方面,相同剂量的DXR静脉给药未观察到抑制肿瘤生长的作用。尽管EO泵和注射器静脉给药对肿瘤生长的抑制作用没有显著差异,但与注射器快速给药相比,EO泵缓慢给药后DXR的外周皮肤浓度降低。这些结果表明,使用EO泵以较慢的给药速率以较低剂量直接i.t.给药DXR可能有助于表现出抗肿瘤作用和抑制全身副作用。此外,与用注射器快速给药后相比,用EO泵以较低速率给药后的DXR的血液浓度和外周皮肤浓度降低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Usefulness of direct intratumoral administration of doxorubicin hydrochloride with an electro-osmosis–assisted pump
Patients receiving chemotherapy by intravenous (i.v.) or oral administration of anticancer drugs often experience side effects. In this study, an electro-osmotic flow (EO) pump was used for the direct administration of an anticancer drug with minimum side effects. Doxorubicin hydrochloride (DXR) was used as an anticancer drug, and its antitumor effect and toxicity were evaluated in comparison with i.v. administration. Balb/c female mice were subcutaneously transplanted with a breast cancer cell line (4T1/Luc) stably expressing luciferase, and 20 μL of DXR solution (1.0 mg/mL) was administered intratumorally (i.t.) at a slow rate (0.6 µL/min) using an EO pump or rapidly using a syringe. For comparison, 100 μL of DXR solution was injected through the tail vein at the same dose and a 5-times higher dose. A tumor growth inhibitory effect without significant weight loss was observed with direct i.t. administration of DXR using an EO pump. On the other hand, no suppressive tumor growth effect was observed with i.v. administration of DXR at the same dose. Although there was no significant difference in the suppression effect on tumor growth between i.t. administration with EO pump and syringe, the peripheral skin concentration of DXR were decreased after slow administration with EO pump compared with that after rapidly administration with a syringe. These results indicated that direct i.t. administration of DXR with lower dosing using an EO pump at slower administration rate may be useful for exhibiting antitumor effects and suppressing systemic side effects. In addition, the blood concentration and the peripheral skin concentration of DXR after administration at lower rate with EO pump were decreased compared with those after the rapidly administration with a syringe.
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