Analytical model of magnetic nanoparticle transport and capture in the microvasculature.

An analytical model is presented for predicting the transport and capture of therapeutic magnetic nanoparticles in the human microvasculature. The nanoparticles, with surface bound drug molecules, are injected into the vascular system upstream from malignant tissue, and are captured at the tumor site using a local applied magnetic field. The applied field is produced by a rare-earth cylindrical magnet positioned outside the body. An analytical expression is derived for predicting the trajectory of a particle as it flows through the microvasculature in proximity to the magnet. In addition, a scaling relation is developed that enables the prediction of the minimum particle radius required for particle capture. The theory takes into account the dominant magnetic and fluidic forces, which depend on the position and properties of the magnet, the size and magnetic properties of the nanoparticles, the dimensions of the microvessel, the hematocrit level of the blood, and the flow velocity. The model is used to study noninvasive drug targeting, and the analysis indicates that submicron particles can be directed to tumors that are several centimeters from the field source.

[1]  M. Takayasu,et al.  Generalization of HGMS theory: The capture of ultra-fine particles , 1983 .

[2]  D. Fletcher,et al.  Fine particle high gradient magnetic entrapment , 1991 .

[3]  I Horikoshi,et al.  Magnetic targeting of thermosensitive magnetoliposomes to mouse livers in an in situ on-line perfusion system. , 1995, Life sciences.

[4]  S. Margel,et al.  Control of magnetophoretic mobility by susceptibility-modified solutions as evaluated by cell tracking velocimetry and continuous magnetic sorting. , 2004, Analytical chemistry.

[5]  Thomas B. Jones,et al.  Electromechanics of Particles , 1995 .

[6]  E. Furlani Permanent Magnet and Electromechanical Devices: Materials, Analysis, and Applications , 2001 .

[7]  Carl K. Hoh,et al.  Targeting and retention of magnetic targeted carriers (MTCs) enhancing intra-arterial chemotherapy , 1999 .

[8]  Aleksander S Popel,et al.  Microcirculation and Hemorheology. , 2005, Annual review of fluid mechanics.

[9]  Armin D. Ebner,et al.  Theoretical analysis of a transdermal ferromagnetic implant for retention of magnetic drug carrier particles , 2005 .

[10]  S. Goodwin,et al.  Single-dose toxicity study of hepatic intra-arterial infusion of doxorubicin coupled to a novel magnetically targeted drug carrier. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[11]  F. Marcucci,et al.  Active targeting with particulate drug carriers in tumor therapy: fundamentals and recent progress. , 2004, Drug discovery today.

[12]  M. Takayasu,et al.  Magnetic separation of submicron particles , 1983 .

[13]  Q. Pankhurst,et al.  Applications of magnetic nanoparticles in biomedicine , 2003 .

[14]  S. Margel,et al.  Establishment and implications of a characterization method for magnetic nanoparticle using cell tracking velocimetry and magnetic susceptibility modified solutions. , 2005, The Analyst.

[15]  C Alexiou,et al.  Clinical applications of magnetic drug targeting. , 2001, The Journal of surgical research.

[16]  A. Pries,et al.  Biophysical aspects of blood flow in the microvasculature. , 1996, Cardiovascular research.

[17]  J. Gallo,et al.  Enhanced brain tumor selectivity of cationic magnetic polysaccharide microspheres. , 1998, Journal of drug targeting.

[18]  J. Gallo,et al.  Distribution of Small Magnetic Particles in Brain Tumor-bearing Rats , 2004, Journal of Neuro-Oncology.

[19]  Catherine C. Berry,et al.  Functionalisation of magnetic nanoparticles for applications in biomedicine , 2003 .

[20]  P Reichardt,et al.  Clinical experiences with magnetic drug targeting: a phase I study with 4'-epidoxorubicin in 14 patients with advanced solid tumors. , 1996, Cancer research.

[21]  Armin D. Ebner,et al.  Analysis of magnetic drug carrier particle capture by a magnetizable intravascular stent—2: Parametric study with multi-wire two-dimensional model , 2005 .

[22]  C. Alexiou,et al.  Locoregional cancer treatment with magnetic drug targeting. , 2000, Cancer research.

[23]  Armin D. Ebner,et al.  Application of high gradient magnetic separation principles to magnetic drug targeting , 2004 .

[24]  Norval J. C. Strachan,et al.  Modelling magnetic carrier particle targeting in the tumor microvasculature for cancer treatment , 2005 .