Mathematical modelling of drug delivery to solid tumour

Effective delivery of therapeutic agents to tumour cells is essential to the success of most cancer treatment therapies except for surgery. The transport of drug in solid tumour involves multiple biophysical and biochemical processes which are strongly dependent on the physicochemical properties of the drug and biological properties of the tumour. Owing to the complexities involved, mathematical models are playing an increasingly important role in identifying the factors leading to inadequate drug delivery to tumours. In this study, a computational model is developed which incorporates real tumour geometry reconstructed from magnetic resonance images, drug transport through the tumour vasculature and interstitial space, as well as drug uptake by tumour cells. The effectiveness of anticancer therapy is evaluated based on the percentage of survival tumour cells by directly solving the corresponding pharmacodynamics equation using predicted intracellular drug concentration. Computational simulations have been performed for the delivery of doxorubicin through various delivery modes, including bolus injection and continuous infusion of doxorubicin in free form, and thermo-sensitive liposome mediated doxorubicin delivery activated by high intensity focused ultrasound. Predicted results show that continuous infusion is far more effective than bolus injection in maintaining high levels of intracellular drug concentration, thereby increasing drug uptake by tumour cells. Moreover, multiple-administration is found to be more effective in improving the cytotoxic effect of drug compared to a single administration. The effect of heterogeneous distribution of microvasculature on drug transport in a realistic model of liver tumour is investigated, and the results indicate that although tumour interstitial fluid pressure is almost uniform, drug concentration is sensitive to the heterogeneous distribution of microvasculature within a tumour. Results from three prostate tumours of different sizes suggest a nonlinear relationship between transvascular transport of anticancer drugs and tumour size. Numerical simulations of thermo-sensitive liposome-mediated drug delivery coupled with high intensity focused ultrasound heating demonstrate the potential advantage of this novel drug delivery system for localised treatment while minimising drug concentration in normal tissue.Open Acces

Effects of Focused-Ultrasound-and-Microbubble-Induced Blood-Brain Barrier Disruption on Drug Transport under Liposome-Mediated Delivery in Brain Tumour : a Pilot Numerical Simulation Study

Funding: This research received no external funding. Acknowledgments: The author would like to acknowledge the supports of the Imperial College London Central Library and the Maxwell Compute Cluster funded by the University of Aberdeen.Peer reviewedPublisher PD

Convection enhanced delivery of anti-angiogenic and cytotoxic agents in combination therapy against brain tumour

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Mathematical modelling of nanoparticle-mediated topical drug delivery to skin tissue

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Mathematical modelling of microneedle-mediated transdermal delivery of drug nanocarriers into skin tissue and circulatory system

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Numerical simulation of transdermal delivery of drug nanocarriers using solid microneedles and medicated adhesive patch

Open Access via the Elsevier agreementPeer reviewedPublisher PD

A Mathematical Model for Thermosensitive Liposomal Delivery of Doxorubicin to Solid Tumour

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Multiphysics Simulation in Drug Development and Delivery

open access via springer compact agreementPeer reviewedPublisher PD

ORIGIN OF LARGE CARBONATE CONCRETIONS IN THE HURON MEMBER OF THE OHIO SHALE (DEVONIAN), CENTRAL OHIO

Large carbonate concretions are a prominent feature of the lower Huron Member of the Ohio Shale, a classic Devonian black shale, of Ohio. The origin of the carbonate concretions, and their growth history, has long remained largely unknown. The purpose of this study was to determine the mineralogy and interpret the early diagenesis of the concretions, with the ultimate aim of gaining insight into the early taphonomic history of organisms preserved in them. Specimens studied are from Franklin and Delaware counties, Ohio. Concretions were studied in the field, and in the laboratory using Scanning Electron Microscopy/Electron Dispersive Spectroscopy (SEM/EDS), and X-ray Diffraction (XRD) technology. XRD analysis reveals that the concretions are differentiated into three parts by distinct mineralogical differences. The inner core region consists largely of barite and calcium phosphate. The outer core is formed mostly of calcite and notable amount of quartz, and the outer rings (non-core zone) are composed largely of ankerite. The concretions thus seem to have experienced multiple growth phases. SEM analysis shows that some concretions have fossils resembling algae. The fossils are preserved in silica, which may be secondary after carbonate. The fossils were likely responsible in part for nucleating the concretions. The presence of calcium phosphate in the inner cores of concretions suggests that decaying animals also may have played a role in nucleating the Ohio Shale carbonate concretions.The Friends of Orton Hall FundThe Zinni Family Field Camp Scholarship FundNo embargoAcademic Major: Earth Science

The effect of tumour size on drug transport and uptake in 3-D tumour models reconstructed from magnetic resonance images

This work was partially funded by the UK Engineering and Physics Sciences Research Council (EP/I001700/1) to XYX. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD