Selected Preclinical and First Clinical Experiences with Magnetically Targeted 4’-Epidoxorubicin in Patients with Advanced Solid Tumors

Lübbe, Andreas S.; Bergemann, Christian

doi:10.1007/978-1-4757-6482-6_35

Cited by 196 publications

(283 citation statements)

References 12 publications

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“…This problem is relevant to magnetically targeted drug and gene delivery whereby therapeutic drugs and/or genes are attached to biocompatible magnetic nanoparticles, or magnetically loaded macrophages and injected into the blood (a concentrated suspension of red blood cells). A magnetic force is then applied with the aim of guiding the magnetic particles/macrophages to a target site [12,18,19,20,21]. The body force exerted on the particles leads to them being transported with velocities significantly different to that of the flow and, in particular, to a trans-stream component of velocity that can enhance their deposition on the vessel wall.…”

Section: Discussionmentioning

confidence: 99%

“…[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%

“…These include techniques that rely on magnetic targeting using, for example, magnetic microparticles (recently reviewed by Dobson [6] and by Pankhurst et al [21]) and magnetically tagged macrophages (Muthana et al [20]) as the transport vehicle. 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]).…”

Section: Introductionmentioning

confidence: 99%

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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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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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Section: Discussionmentioning

confidence: 99%

“…[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%

Section: Introductionmentioning

confidence: 99%

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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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“…Magnetic targeting exploits paramagnetic particles as drug carriers, guides their accumulation in target tissues with local strong magnetic fields, and has been used with some success in the treatment of cancer patients. 6 Applying this principle to gene vectors, given the rationale, would set the basis for a method of auto- matizable high throughput transfection in vitro and, more importantly, improve their efficacy in vivo. Both goals would require rapid transfection kinetics, greatly improved dose-response characteristics and the possibility of vector targeting to a selected area.…”

Section: Introductionmentioning

confidence: 99%

Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo

et al. 2002

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“…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. 11,[15][16][17] Though these studies have provided proof that the MDT application has promise as a clinical modality, only a few physics-based works have examined the interaction of the ferrofluid aggregate with an incident non-magnetic flow. Understanding the governing physics and scaling of the ferrofluid dispersion and retention could aid in the development of improved MDT methodologies.…”

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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Selected Preclinical and First Clinical Experiences with Magnetically Targeted 4’-Epidoxorubicin in Patients with Advanced Solid Tumors

Cited by 196 publications

References 12 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

Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo

Dispersion of ferrofluid aggregates in steady flows

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