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MICRO/NANOSCALE HEAT TRANSFER—PART II

Numerical Study of Thermally Targeted Liposomal Drug Delivery in Tumor

[+] Author and Article Information
Aili Zhang, Xipeng Mi, Geer Yang

Department of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China

Lisa X. Xu

Department of Biomedical Engineering, and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200240, P.R. China

J. Heat Transfer 131(4), 043209 (Feb 24, 2009) (10 pages) doi:10.1115/1.3072952 History: Received September 09, 2008; Revised December 09, 2008; Published February 24, 2009

The efficacy of cancer chemotherapy can be greatly enhanced by thermally targeted nanoparticle liposome drug delivery system. A new theoretical model coupling heat and mass transfer has been developed to study the spatial and transient drug distributions. In this model, the influence of tumor cell apoptosis and necrosis in drug transport is also considered, in addition to the tumor microvasculature permeability to nanoliposomes. The model predictions agree well with our previous experimental results, and it has been used to simulate the nanoparticle drug distribution in the tumor under hyperthermic conditions. Results show that hyperthermia alone only enhances drug accumulation in the periphery of a tumor with 1 cm in radius, and the tumor cells in the central region are hardly damaged due to poor drug diffusion. Apoptosis or necrosis of the tumor cells could significantly influence the drug penetration and should be accounted for in drug diffusion modeling to accurately predict the therapeutic effect. Simulation study on the combined radio frequency ablation and liposomal doxorubicin delivery shows more effective treatment outcome, especially for larger tumors. The present model can be used to predict the treatment outcome and optimize the clinical protocol.

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Copyright © 2009 by American Society of Mechanical Engineers
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Figures

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Figure 8

The effect of cell necrosis induced diffusivity change on tumor therapy: (1) with cell necrosis induced diffusivity change considered; (2) without consideration of cell necrosis induced diffusivity change

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Figure 9

Temperature distribution in the tumor after 30 min of the RF heating at 10 W; radius represents the distance measured from the RF probe

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Figure 10

Simulation results of drug concentrations and cell survival rate distribution in a 1 cm tumor under the combined RF ablation with the liposome drug treatment, where: the central region (0–2.5 mm), the peripheral region (2.5–5 mm), and the normal tissue (5–10 mm). Heating power is 10 W.

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Figure 11

Simulation results of drug concentrations and cell survival rates in a 3 cm diameter tumor under various powers of the RF heating. (a) Concentration of the liposome drug in tumor right after the RF heating, (b) tumor cell survival rates in 7 days after the combined treatments for different powers of the RF heating and different half-life times of liposome drug, where: the central region (0–7.5 mm), the peripheral region (7.5–15 mm), and the normal tissue (15–30 mm).

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Figure 12

The total volume of the tumor cells with the survival rate lower than 0.1% after the RF ablation alone and the combined treatment using different heating powers

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Figure 1

Vasculature fluorescent images in the tumor center and periphery before and after thermal treatments. Bar: 200 μm. (a) and (b): before treatment and (c) and (d): heated at 42°C for 1 h (8).

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Figure 7

The effect of liposome rupture time τr on drug delivery and tumor therapy: (a) average survival rate in the central region of the tumor and (b) average survival rate in the peripheral region of the tumor

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Figure 2

HT-induced extravasation of 100 nm liposome nanoparticles at 42°C or 34°C for 1 h in different tumor regions. The largest HT enhancement of extravasation was seen at tumor periphery. Values are mean and standard error (SE) (n=11 for each group) (8).

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Figure 3

Schematics of the tumor, I: central region of the tumor, II: peripheral region of the tumor, and III: surrounding normal tissue

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Figure 4

Simulation results of drug concentration and cell survival rate in the tumor after 1 h liposomal drug delivery aided by hyperthermia at 42°C, where: the central region (0–0.6 mm), the peripheral region (0.6–1.0 mm), and the surrounding normal tissue (1.0–2.0 mm)

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Figure 5

Simulation results of drug concentrations and cell survival rate in a 1 cm tumor without hyperthermia, where: the central region (0–6 mm), the peripheral region (6–10 mm), and the surrounding normal tissue (10–20 mm)

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Figure 6

Simulation results of drug concentrations and cell survival rate in a 1 cm tumor with hyperthermia, where: the central region (0–6 mm), the peripheral region (6–10 mm), and the surrounding normal tissue (10–20 mm)

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