利用微透析技术进行二氢卟吩e6磁性声敏脂质体的肿瘤局部药动学研究

Local Pharmacokinetics of Chlorin e6-loaded Magnetic Ultrasound-sensitive Liposomes in Tumor Tissue Based on Microdialysis Technique

以载声敏剂二氢卟吩e6(Ce6)的磁性声敏脂质体(Ce6-MUL)作为声动力疗法(SDT)的研究对象,通过裸鼠转移SPCA-1肺腺癌模型考察其在磁场和超声作用下在肿瘤局部的药动学特征。利用微透析采样技术收集肿瘤局部的透析液,再用HPLC法测定药物浓度。对比研究了Ce6-MUL不加磁场组和加磁场组、游离Ce6生理盐水溶液(加磁场)和Ce6-MUL加磁场及超声组裸鼠肿瘤局部的药物浓度及主要药动学参数。结果显示,上述4组的t1/2分别为(3.26±0.98)、(4.47±0.78)、(2.47±0.66)、(4.67±0.72)h,AUC0→∞分别为(18.17±1.24)、(25.82±3.12)、(7.18±1.83)、(28.22±4.41)mg·L-1·h,MRT0→∞分别为(6.28±0.67)、(6.88±0.59)、(4.79±0.74)、(7.05±1.00)h,提示Ce6-MUL在外加磁场作用下可靶向于肿瘤组织,结合SDT能显著提高药物浓度,可能有利于提高Ce6的抗肿瘤活性。

The local pharmacokinetics of the magnetic ultrasound-sensitive liposomes(MUL),loaded with sonosensitizer chlorin e6(Ce6),as the model drug combined with sonodynamic therapy(SDT)was investigated in a Xenograft model of lung adenocarcinoma with magnetic field and ultrasound treatments.The drug concentration in dialysate collected by microdialysis sampling technique was determined by HPLC.The drug concentrations in tumor tissue and main pharmacokinetic parameters of four test groups,namely Ce6-MUL without and with magnetic field treatment,Ce6 saline solution with magnetic field treatment and Ce6-MUL with both magnetic field and ultrasound treatments,were compared.The main calculated parameters for the four groups were as follows:t1/2 were(3.26±0.98),(4.47±0.78),(2.47±0.66)and(4.67±0.72)h;AUC0→∞were(18.17±1.24),(25.82±3.12),(7.18±1.83)and(28.22±4.41)mg·L-1·h;MRT0→∞were(6.28±0.67),(6.88±0.59),(4.79±0.74)and(7.05±1.00)h,respectively.It was concluded that Ce6-MUL could be accumulated in tumor tissue under the action of an external magnetic field;the drug concentration in tumor tissue was significantly increased by the combination effect of magnetic field and ultrasound,which might be helpful to improve the anti-tumor activity of Ce6.