Magnetic nanoparticles encapsulated into biodegradable microparticles steered with an upgraded magnetic resonance imaging system for tumor chemoembolization

Pouponneau, Pierre; Leroux, Jean‐Christophe; Martel, Sylvain

doi:10.1016/j.biomaterials.2009.08.005

Cited by 126 publications

(69 citation statements)

References 35 publications

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“…Furthermore, the therapeutic agents can fail to destroy enough tumor cells to prevent development of new hepatocellular carcinoma. Pouponneau et al 32 recently proposed the use of magnetic nanoparticles, in enhancement to the traditional trans-arterial embolizing methods, where the injected nanoparticles are guided in real time via magnetic resonance imaging. This image-guided drug delivery method has a caveat that ultrafine particles delivered to the system carry the potential for uncontrolled diffusivity and adverse embolizations distal to the tumor sites.…”

Section: Introductionmentioning

confidence: 99%

Computer Modeling of Controlled Microsphere Release and Targeting in a Representative Hepatic Artery System

et al. 2010

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Combating liver tumors via yttrium-90 ((90)Y) radioembolization is a viable treatment option of nonresectable liver tumors. Employing clinical (90)Y microparticles (i.e., SIR-Spheres and TheraSpheres) in a computational model of a representative hepatic artery system, laminar transient 3D particle-hemodynamics were simulated. Specifically, optimal particle release positions in the right hepatic (parent) artery as well as the best temporal release window were determined for the microspheres to exit specific outlet daughter vessels, potentially connected to liver tumors. The results illustrate the influence of a curved geometry on the velocity field and the particle trajectory dependence on the spatial and temporal particle injection conditions. The differing physical particle characteristics of the SIR-Spheres and the TheraSpheres had a subtle impact on particle trajectories in the decelerating portion of the arterial pulse, i.e., when the inertial forces on the particles are weaker. Conversely, particle characteristics and inelastic wall collisions had little effect on particles released during the accelerating phase of the arterial pulse, i.e., both types of microspheres followed organized paths to predetermined outlets. Such results begin paving the way towards directing 100% of the released microspheres to specific daughter vessels (e.g., those connected to tumors) under transient flow conditions in realistic geometries via a novel drug-particle targeting methodology.

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Section: Introductionmentioning

confidence: 99%

Computer Modeling of Controlled Microsphere Release and Targeting in a Representative Hepatic Artery System

et al. 2010

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“…After this discovery, researchers began engineering microspheres (MSs) to deliver drugs with poor water solubility (8)(9)(10), poor gastrointestinal permeability (11), or poor oral bioavailability (8,9,(12)(13)(14)(15) to the small intestine. MS-based oral drug delivery systems (ODDSs) can be made from biodegradable polymers (12,(16)(17)(18), nondegradable polymers (19)(20)(21), and polysaccharides (22,23) and can be engineered to carry polypeptides (18,24,25) and other molecules (26,27). The motivation for using microparticulate-based ODDSs is to improve the oral bioavailability of drugs by enhancing their delivery and transit through the absorptive epithelium of the small intestine.…”

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confidence: 99%

Unique insights into the intestinal absorption, transit, and subsequent biodistribution of polymer-derived microspheres

Reineke

Cho

Dingle

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Polymeric microspheres (MSs) have received attention for their potential to improve the delivery of drugs with poor oral bioavailability. Although MSs can be absorbed into the absorptive epithelium of the small intestine, little is known about the physiologic mechanisms that are responsible for their cellular trafficking. In these experiments, nonbiodegradable polystyrene MSs (diameter range: 500 nm to 5 μm) were delivered locally to the jejunum or ileum or by oral administration to young male rats. Following administration, MSs were taken up rapidly (≤5 min) by the small intestine and were detected by transmission electron microscopy and confocal laser scanning microscopy. Gel permeation chromatography confirmed that polymer was present in all tissue samples, including the brain. These results confirm that MSs (diameter range: 500 nm to 5 μm) were absorbed by the small intestine and distributed throughout the rat. After delivering MSs to the jejunum or ileum, high concentrations of polystyrene were detected in the liver, kidneys, and lungs. The pharmacologic inhibitors chlorpromazine, phorbol 12-myristate 13-acetate, and cytochalasin D caused a reduction in the total number of MSs absorbed in the jejunum and ileum, demonstrating that nonphagocytic processes (including endocytosis) direct the uptake of MSs in the small intestine. These results challenge the convention that phagocytic cells such as the microfold cells solely facilitate MS absorption in the small intestine.oral delivery | uptake mechanism B eginning in the 1960s, several groups (1-7) demonstrated that the small intestine could absorb microparticles with a diameter >1 μm, challenging dogma that the small intestine could only absorb small macromolecules. After this discovery, researchers began engineering microspheres (MSs) to deliver drugs with poor water solubility (8-10), poor gastrointestinal permeability (11), or poor oral bioavailability (8,9,(12)(13)(14)(15) to the small intestine. MS-based oral drug delivery systems (ODDSs) can be made from biodegradable polymers (12,(16)(17)(18), nondegradable polymers (19-21), and polysaccharides (22, 23) and can be engineered to carry polypeptides (18,24,25) and other molecules (26, 27). The motivation for using microparticulate-based ODDSs is to improve the oral bioavailability of drugs by enhancing their delivery and transit through the absorptive epithelium of the small intestine. This work may ultimately enable patients to take medications orally instead of relying on daily or weekly injections or other, less convenient routes of administration (28).More than five decades after Sanders and Ashworth discovered that the small intestine can engulf large particles (1), little is known today about the cellular mechanisms or physiologic pathways that facilitate the absorption, transit, and biodistribution of microparticles that are delivered to the small intestine. Nonetheless, the diverse physiology and multitude of cell types in the small intestine likely play a central role in these processes. The absorp...

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“…Nevertheless, it was also reported that carbon microparticles of size in the range 0.5÷5 µm may potentially be used for in vivo applications e.g. chemotherapy [2,8]. In this case other routes of administration to targeted place are required including intra-arterial administration [2] or catheterization [3,8,9].…”

Section: Introductionmentioning

confidence: 99%

“…chemotherapy [2,8]. In this case other routes of administration to targeted place are required including intra-arterial administration [2] or catheterization [3,8,9]. The latter method is based on the placement of magnetic microparticles in the blood vessel, which feeds the tumour and subsequently their transportation by a magnetic field forces into the cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Magnetic nanocomposites for biomedical applications

Izydorzak-Woźniak

Leonowicz

2015

Mechanik

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Magnetic carbon nanocomposites (MCNCs), with different constitution and fractions of magnetic component, were fabricated by the pyrolysis of the polymeric precursor. X-ray diffraction, transmission electron microscopy and Raman spectroscopy revealed the presence of nanocrystallites (NCs) of Co, Fe 3 C and Ni embedded in porous, partially graphitized carbon matrix. Vibrating sample magnetometer measurements enabled to determine the correlation between NCs size distribution and magnetic properties. The magnetic studies confirmed that the coercivity, saturation and remanent magnetizations, as well as fraction of the magnetic component depend on the pyrolysis temperature. The Co#C and Fe 3 C#C composites exhibited ferromagnetic behaviour with a remanent to saturation magnetization (M R /M S ) ratio ranging from 0.25 to 0.3, whereas in the Ni containing samples a relatively small M R /M S ratio points to significant contribution of superparamagnetic interactions. The Ni#C composites, having superparamagnetic and/or ferromagnetic nanocrystallites in their volume, were chosen to check the ability of heat generation in a magnetic field. It was found that the hysteresis losses were the main mechanism of heat generation. The MCNCs obtained can potentially be applied for hyperthermia treatment. As the MCNCs are proposed for biomedical application the basic cytotoxicity test were performed to evaluate a potential toxic effect of the materials on MG-63 cells line. The test results confirmed that the composites containing Fe 3 C are non-cytotoxic whereas the majority of the Ni#C and Co#C composites was characterized as slightly or moderately cytotoxic. Keywords: magnetic carbon nanocomposite, magnetic properties, pyrolysis, cytotoxicity, biomedicine

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Magnetic nanoparticles encapsulated into biodegradable microparticles steered with an upgraded magnetic resonance imaging system for tumor chemoembolization

Cited by 126 publications

References 35 publications

Computer Modeling of Controlled Microsphere Release and Targeting in a Representative Hepatic Artery System

Computer Modeling of Controlled Microsphere Release and Targeting in a Representative Hepatic Artery System

Unique insights into the intestinal absorption, transit, and subsequent biodistribution of polymer-derived microspheres

Magnetic nanocomposites for biomedical applications

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