Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes

<italic>Goal:</italic> The impact of hyperthermia (HT) method on tumor drug uptake with thermosensitive liposomes (TSL) is not well understood. <italic>Methods:</italic> We created realistic three-dimensional (3-D) computer models that simulate TSL-encapsulated doxorubicin (T...

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Main Authors: Krishna Ramajayam, A. Wolfe, Anjan Motamarry, Georges Nahhas, John Yost, Michael Yost, Dieter Haemmerich
Format: Article
Language:English
Published: IEEE 2021-01-01
Series:IEEE Open Journal of Engineering in Medicine and Biology
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Online Access:https://ieeexplore.ieee.org/document/9428538/
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author Krishna Ramajayam
A. Wolfe
Anjan Motamarry
Georges Nahhas
John Yost
Michael Yost
Dieter Haemmerich
author_facet Krishna Ramajayam
A. Wolfe
Anjan Motamarry
Georges Nahhas
John Yost
Michael Yost
Dieter Haemmerich
author_sort Krishna Ramajayam
collection DOAJ
description <italic>Goal:</italic> The impact of hyperthermia (HT) method on tumor drug uptake with thermosensitive liposomes (TSL) is not well understood. <italic>Methods:</italic> 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 <italic>in vivo</italic> studies. <italic>Results:</italic> Average computer model-predicted tumor drug concentrations (&#x03BC;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 &#x00D7; (T) and 1.6 &#x00D7; (L) when HT duration was extended from 15 to 60 min (p &lt; 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. <italic>Conclusions:</italic> Untargeted large volume HT causes poor tumor drug uptake from TSL.
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spelling doaj-art-16c794f038424a39be8bb48bf8db18c12025-08-20T03:32:40ZengIEEEIEEE Open Journal of Engineering in Medicine and Biology2644-12762021-01-01218719710.1109/OJEMB.2021.30788439428538Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive LiposomesKrishna Ramajayam0A. Wolfe1Anjan Motamarry2Georges Nahhas3John Yost4Michael Yost5Dieter Haemmerich6https://orcid.org/0000-0003-1127-7024Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USARalph H. Johnson VA Medical Center, Charleston, SC, USADepartment of Pediatrics, Medical University of South Carolina, Charleston, SC, USAHollings Cancer Center, Medical University of South Carolina, Charleston, SC, USADepartment of Surgery, Medical University of South Carolina, Charleston, SC, USADepartment of Surgery, Medical University of South Carolina, Charleston, SC, USADepartment of Pediatrics, Medical University of South Carolina, Charleston, SC, USA<italic>Goal:</italic> The impact of hyperthermia (HT) method on tumor drug uptake with thermosensitive liposomes (TSL) is not well understood. <italic>Methods:</italic> 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 <italic>in vivo</italic> studies. <italic>Results:</italic> Average computer model-predicted tumor drug concentrations (&#x03BC;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 &#x00D7; (T) and 1.6 &#x00D7; (L) when HT duration was extended from 15 to 60 min (p &lt; 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. <italic>Conclusions:</italic> Untargeted large volume HT causes poor tumor drug uptake from TSL.https://ieeexplore.ieee.org/document/9428538/Computer modelsdrug deliveryhyperthermia (HT)<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</italic>thermosensitive liposomes
spellingShingle Krishna Ramajayam
A. Wolfe
Anjan Motamarry
Georges Nahhas
John Yost
Michael Yost
Dieter Haemmerich
Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes
IEEE Open Journal of Engineering in Medicine and Biology
Computer models
drug delivery
hyperthermia (HT)
<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</italic>
thermosensitive liposomes
title Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes
title_full Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes
title_fullStr Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes
title_full_unstemmed Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes
title_short Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes
title_sort untargeted large volume hyperthermia reduces tumor drug uptake from thermosensitive liposomes
topic Computer models
drug delivery
hyperthermia (HT)
<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</italic>
thermosensitive liposomes
url https://ieeexplore.ieee.org/document/9428538/
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