非靶向大体积热疗降低热敏脂质体的肿瘤药物摄取量。

Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes.

作者信息

Ramajayam Krishna K, Wolfe A Marissa, Motamarry Anjan, Nahhas Georges J, Yost John, Yost Michael J, Haemmerich Dieter

机构信息

Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425 USA.

Ralph H. Johnson VA Medical Center, Charleston, SC 29401 USA.

出版信息

IEEE Open J Eng Med Biol. 2021;2:187-197. doi: 10.1109/ojemb.2021.3078843. Epub 2021 May 11.

GOAL

The impact of hyperthermia (HT) method on tumor drug uptake with thermosensitive liposomes (TSL) is not well understood.

METHODS

We created realistic three-dimensional (3-D) computer models that simulate TSL-encapsulated doxorubicin (TSL-DOX) delivery in mouse tumors with three HT methods (thermistor probe (T), laser (L) and water bath (WB), at 15 min and 60 min HT duration), with corroborating studies.

RESULTS

Average computer model-predicted tumor drug concentrations (g/g) were 8.8(T, 15 min), 21.0(T, 60 min), 14.1(L, 15 min), 25.2(L, 60 min), 9.4(WB, 15 min), and 8.7(WB, 60 min). Tumor fluorescence was increased by 2.6 × (T) and 1.6 × (L) when HT duration was extended from 15 to 60 min (p 0.05), with no increase for WB HT. Pharmacokinetic analysis confirmed that water bath HT causes rapid depletion of encapsulated TSL-DOX in systemic circulation due to the large heated tissue volume.

CONCLUSIONS

Untargeted large volume HT causes poor tumor drug uptake from TSL.

目的

热疗（HT）方法对热敏脂质体（TSL）介导的肿瘤药物摄取的影响尚未完全明确。

方法

我们创建了逼真的三维（3-D）计算机模型，模拟了三种热疗方法（热敏电阻探头（T）、激光（L）和水浴（WB），热疗持续时间分别为15分钟和60分钟）下，TSL包裹的阿霉素（TSL-DOX）在小鼠肿瘤中的递送情况，并进行了相关研究加以佐证。

结果

计算机模型预测的肿瘤平均药物浓度（克/克）分别为：8.8（T，15分钟）、21.0（T，60分钟）、14.1（L，15分钟）、25.2（L，60分钟）、9.4（WB，15分钟）和8.7（WB，60分钟）。当热疗持续时间从15分钟延长至60分钟时，肿瘤荧光强度增加了2.6倍（T）和1.6倍（L）（p<0.05），而水浴热疗时荧光强度无增加。药代动力学分析证实，由于加热组织体积较大，水浴热疗会导致全身循环中包裹的TSL-DOX迅速耗尽。