In vitro and in vivo investigations of targeted chemotherapy with magnetic nanoparticles

Motivated by the technology of magnetically targeted drug and gene delivery, in which a magnetic field is used to direct magnetic carrier particles from the circulation to a target site, we develop a continuum model for the motion of particles (magnetic carriers) subject to an external body force (magnetic field) in a flow of a concentrated suspension of a species of neutrally buoyant particles (blood). An advection-diffusion equation describes the evolution of the carrier particles as they advect in the flow under the action of an external body force, and diffuse as a result of random interactions with the suspension of neutrally buoyant particles (shear-induced diffusion). The model is analysed for the case in which there is steady Poiseuille flow in a cylindrical vessel, the diffusive effects are weak and there is weak carrier uptake along the walls of the vessel. The method of matched asymptotic expansions is used to show that carriers are concentrated in a boundary layer along the vessel wall and, further, that there is a carrier flux along this layer which results in a sub-layer, along one side of the vessel, in which carriers are even more highly concentrated. Three distinguished limits are identified: they correspond to cases for which (i) the force is sufficiently weak that most particles move through the vessel without entering the boundary layers along the walls of the vessel and (ii) and (iii) to a force which is sufficiently strong that a significant fraction of the particles enter the boundary layers and, depending upon the carrier absorption from the vessel walls, there is insignificant/significant axial carrier flux in these layers.

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“…[9]), magnetically targeted drug and gene delivery (e.g. [2,3,6,12,18,19,20,21]), as well as separation under gravity (e.g. [5]).…”

Section: Introductionmentioning

confidence: 99%

“…In the context of the former, and older technology, there have been two Phase I/II clinical trials [18,28] in addition to numerous in vivo studies (e.g. [2,3,19]). While the latter, newer technology has only been subject to a single combined in vitro and in vivo trial [20], it shows great promise.…”

Section: Introductionmentioning

confidence: 99%

Particle trapping by an external body force in the limit of large Peclet number: applications to magnetic targeting in the blood flow

Richardson¹,

Kaouri

Byrne

2010

Eur. J. Appl. Math

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“…For example, magnetic nanoparticles have recently received much attention due to their potential application in clinical cancer treatment, [158][159][160][161][162] targeted drug delivery [163][164][165] and MRI contrast agents. 166,167 However, despite the useful functionalities that might derive from metal nanoparticle systems, the lack of targeting strategies has limited their application to locoregional disease.…”

Section: Future Applicationsmentioning

confidence: 99%

Transductional targeting of adenovirus vectors for gene therapy

2006

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“…10 Some of the newest ferrofluid applications have been focused on their integration in a new technique for targeting disease treatment in the human body. [11][12][13][14][15] Magnetic drug targeting (MDT) involves magnetically guiding droplets of a biocompatible ferrofluid bonded reversibly to specific chemotherapeutic agents, which are injected into the blood or lymphatic circulation system. 15 Some trials performed on lab animals have shown that 50% of the typical systemic dose applied to treat cancerous tumors can result in remission of the tumor after only one treatment of anticancer drugs with MDT.…”

Section: Introductionmentioning

confidence: 99%

Dispersion of ferrofluid aggregates in steady flows

Williams

Vlachos

2011

Physics of Fluids

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Using focused shadowgraphs, we investigate steady flows of a magnetically non-susceptible fluid interacting with ferrofluid aggregates comprised of superparamagnetic nanoparticles. The ferrofluid aggregate is retained at a specific site within the flow channel using two different applied magnetic fields. The bulk flow induces shear stresses on the aggregate, which give rise to the development of interfacial disturbances, leading to Kelvin-Helmholtz (K-H) instabilities and shedding of ferrofluid structures. Herein, the effects of bulk Reynolds number, ranging from 100 to 1000, and maximum applied magnetic fields of 1.2 × 105 and 2.4 × 105 A/m are investigated in the context of their impact on dispersion or removal of material from the core aggregate. The aggregate interaction with steady bulk flow reveals three regimes of aggregate dynamics over the span of Reynolds numbers studied: stable, transitional, and shedding. The first regime is characterized by slight aggregate stretching for low Reynolds numbers, with full aggregate retention. As the Reynolds number increases, the aggregate is in-transition between stable and shedding states. This second regime is characterized by significant initial stretching that gives way to small amplitude Kelvin-Helmholtz waves. Higher Reynolds numbers result in ferrofluid shedding, with Strouhal numbers initially between 0.2 and 0.3, wherein large vortical structures are shed from the main aggregate accompanied by precipitous decay of the accumulated ferrofluid aggregate. These behaviors are apparent for both magnetic field strengths, although the transitional Reynolds numbers are different between the cases, as are the characteristic shedding frequencies relative to the same Reynolds number. In the final step of this study, relevant parameters were extracted from the time series dispersion data to comprehensively quantify aggregate mechanics. The aggregate half-life is found to decrease as a function of the Reynolds number following a power law curve and can be scaled for different magnetic fields using the magnetic induction at the inner wall of the vessel. In addition, the decay rate of the ferrofluid is shown to be proportional to the wall shear rate. Finally, a dimensionless parameter, which scales the inertia-driven flow pressures, relative to the applied magnetic pressures, reveals a power law decay relationship with respect to the incident bulk flow.

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In vitro and in vivo investigations of targeted chemotherapy with magnetic nanoparticles

Cited by 166 publications

References 9 publications

Particle trapping by an external body force in the limit of large Peclet number: applications to magnetic targeting in the blood flow

Particle trapping by an external body force in the limit of large Peclet number: applications to magnetic targeting in the blood flow

Transductional targeting of adenovirus vectors for gene therapy

Dispersion of ferrofluid aggregates in steady flows

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