Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes

• Published in: IEEE open journal of engineering in medicine and biology Vol. 2; pp. 187 - 197
• Main Authors: Ramajayam, Krishna, Wolfe, A., Motamarry, Anjan, Nahhas, Georges, Yost, John, Yost, Michael, Haemmerich, Dieter
• Format: Journal Article
• Language: English
• Published: United States IEEE 01.01.2021; The Institute of Electrical and Electronics Engineers, Inc. (IEEE)
• Subjects: <italic xmlns:ali="http://www.niso.org/schemas/ali/1.0/" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">in vivo; Computational modeling; Computer models; Depletion; Doxorubicin; drug delivery; Drugs; Encapsulation; Fluorescence; Heating systems; Hyperthermia; hyperthermia (HT); In vivo methods and tests; Laser modes; Liposomes; Mathematical models; Pharmacokinetics; Thermistors; thermosensitive liposomes; Three dimensional models; Tumors; Water baths; Water circulation; Water heating; Computer models; in vivo; drug delivery; hyperthermia (HT); thermosensitive liposomes
• ISSN: 2644-1276; 2644-1276
• DOI: 10.1109/OJEMB.2021.3078843

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 in vivo studies. Results: Average computer model-predicted tumor drug concentrations (μg/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.