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Pharmacokinetics Approach for Nanotoxicity Evaluation
Published in Vineet Kumar, Nandita Dasgupta, Shivendu Ranjan, Nanotoxicology, 2018
The multi-compartment model is constructed to express the pharmacokinetics of drug molecules with more than two compartments. In this model, each individual compartment is constructed to resemble all the important organs/barriers involved in the ADME of the drug. It represents the most exhaustive model considering the complexity in transport mechanism of drug molecules, including its elimination from the body. The log Cp vs time plot shows a multiphase response. The concentration versus time plot exhibits multiple exponentials, each of which explains its individual compartment (Figure 15.3).
Computational modeling of drug diffusion and inductive heating in an implantable biomedical device for localized thermo-chemotherapy of cancer cells/tissue
Published in Cogent Engineering, 2018
C.J. Ani, Y. Danyuo, O.S. Odusanya, W.O. Soboyejo
Several mathematical and computational models have been developed for the tumor prediction of heating and controlled drug delivery from biomedical devices (Huang & Liauh, 2011; Timko et al., 2014; Weinberg, Patel, Exner, Saidel, & Gao, 2008). These have been used to model the thermal doses (Berjano, 2006), temperature distributions (Huang & Liauh, 2011), and the concentration of drugs released to the tumors or residual tumor cells/tissue (Qian, Stowe, Liu, Saidel, & Gao, 2003). Qian et al. (2003) have developed a mathematical model in the prediction of doxorubicin transport from polymer Milli-rods subjected to radiofrequency-induced thermo-ablation. Their results showed the influence of tissue ablation and devascularization on the transport of doxorubicin. Gasselhuber et al. (2010) used a paired heat transfer and pharmaco-kinetic mathematical model to study drug delivery in a multi-compartment model consisting of low-temperature sensitive liposomes/tumor plasma. They also studied drug delivery in systemic plasma/tissue models. Their simulations showed that the thermal ablation of doxorubicin-loaded liposomes enhanced localized drug delivery into tumor tissue, compared to drug delivery via conventional chemotherapy. Prior work in our research group (Danyuo et al., 2014; Oni et al., 2011) has explored the development of an implantable anti-cancer treatment device that can deliver anticancer drugs locally while heating tumor cells/tissue. Such a device can be used, following surgery, to kill cancer/tumor tissue by localized chemotherapy and hyperthermia. This paper presents the results of a computational study of controlled drug diffusion and hyperthermia from a novel implantable biomedical device for localized cancer therapy (Danyuo et al., 2014; Oni et al., 2011). Finite element model (of the device and surrounding tissue) is developed and used to validate our prior in vitro experimental results (Danyuo et al., 2014). The model is also used to estimate the concentrations of prodigiosin drug released from the smart thermo-sensitive hydrogels via micro-channels to be transported to surrounding cancer cells/tissue. The implications of the results are then discussed in the development of future devices for the localized treatment of cancer/tumor tissue.