Ito Ayu, Itakura Shoko, Hasegawa Yuya, Hashimoto Miyu, Okada Akie, Hirafuji Mamoru, Nakamura Hidenori, Sugibayashi Kenji, Todo Hiroaki
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, Japan.
atDose Co., Ltd., Yokohama, Kanagawa, Japan.
Front Drug Deliv. 2023 Apr 4;3:1150894. doi: 10.3389/fddev.2023.1150894. eCollection 2023.
Patients receiving chemotherapy by intravenous () 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 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 () 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 administration of DXR using an EO pump. On the other hand, no suppressive tumor growth effect was observed with administration of DXR at the same dose. Although there was no significant difference in the suppression effect on tumor growth between 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 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.
通过静脉内（）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，使用电渗流（EO）泵直接给药抗癌药物，使副作用最小化。盐酸多柔比星（DXR）用作抗癌药物，并与给药方式进行比较，评估其抗肿瘤效果和毒性。将稳定表达荧光素酶的乳腺癌细胞系（4T1/Luc）皮下移植到Balb/c雌性小鼠体内，使用EO泵以缓慢速率（0.6 μL/min）或使用注射器快速将20 μL DXR溶液（1.0 mg/mL）瘤内给药（）。作为比较，以相同剂量和高5倍的剂量通过尾静脉注射100 μL DXR溶液。使用EO泵直接瘤内给药DXR观察到肿瘤生长抑制作用且体重无明显减轻。另一方面，相同剂量的DXR给药未观察到肿瘤生长抑制作用。虽然EO泵给药和注射器给药对肿瘤生长的抑制效果没有显著差异，但与注射器快速给药后相比，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泵以较低剂量、较慢给药速率直接瘤内给药DXR可能有助于发挥抗肿瘤作用并抑制全身副作用。此外，与注射器快速给药后相比，EO泵以较低速率给药后DXR的血液浓度和外周皮肤浓度降低。
