MR imaging of biodegradable polymeric microparticles: A potential method of monitoring local drug delivery

Accurate imaging of atherosclerosis is a growing necessity for timely treatment of the disease. Magnetic resonance imaging (MRI) is a promising technique for plaque imaging. The goal of this study was to create polymeric particles of a small size with high loading of diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) and demonstrate their usefulness for MRI. A water-in-oil-in-oil double emulsion solvent evaporation technique was used to encapsulate the MRI agent in a poly(lactide-co-glycolide) (PLGA) or polylactide-poly(ethylene glycol) (PLA-PEG) particle for the purpose of concentrating the agent at an imaging site. PLGA particles with two separate average sizes of 1.83 m and 920 nm, and PLA-PEG particles with a mean diameter of 952 nm were created. Loading of up to 30 wt % Gd-DTPA was achieved, and in vitro release occurred over 5 h. PLGA particles had highly negative zeta potentials, whereas the particles incorporating PEG had zeta potentials closer to neutral. Cytotoxicity of the particles on human umbilical vein endothelial cells (HUVEC) was shown to be minimal. The ability of the polymeric contrast agent formulation to create contrast was similar to that of Gd-DTPA alone. These results demonstrate the possible utility of the contrast agent-loaded polymeric particles for plaque detection with MRI.atherosclerosis ͉ imaging ͉ targeted ͉ PLGA ͉ PEG

Section: Discussionsupporting

confidence: 63%

mentioning

confidence: 99%

Preparation and initial characterization of biodegradable particles containing gadolinium-DTPA contrast agent for enhanced MRI

Doiron

Chu

Ali

et al. 2008

“…However, iron oxide-containing contrast media are in clinical use (39,40), and both we and others (41) are developing micrometer-sized biodegradable particles. Smaller iron oxide particles, such as superparamagnetic particles of iron oxide (SPIO) and ultrasmall SPIO (USPIO), cannot be used for this application owing, in part, to their long half-life (42), which precludes rapid molecular imaging of target-specific binding because of high background levels.…”

Section: Discussionmentioning

confidence: 99%

Molecular MRI enables early and sensitive detection of brain metastases

Serres

Soto

Hamilton

et al. 2012

129

Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MRI contrast agent based on microparticles of iron oxide that enables imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were to determine whether VCAM-1 is up-regulated on vessels associated with brain metastases, and if so, whether VCAM-1-targeted MRI enables early detection of these tumors. Early up-regulation of cerebrovascular VCAM-1 expression was evident on tumor-associated vessels in two separate murine models of brain metastasis. Metastases were detectable in vivo using VCAM-1-targeted MRI 5 d after induction (<1,000 cells). At clinical imaging resolutions, this finding is likely to translate to detection at tumor volumes two to three orders of magnitude smaller (0.3-3 × 10 5 cells) than those volumes detectable clinically (10 7 -10 8 cells). VCAM-1 expression detected by MRI increased significantly (P < 0.0001) with tumor progression, and tumors showed no gadolinium enhancement. Importantly, expression of VCAM-1 was shown in human brain tissue containing both established metastases and micrometastases. Translation of this approach to the clinic could increase therapeutic options and change clinical management in a substantial number of cancer patients.

“…morphology ͉ nanotechnology ͉ geometry ͉ drug delivery ͉ nonspherical P olymeric particles are used in a diverse array of applications including drug delivery (1), advanced materials (2), personal care (3), and medical imaging (4). They also are used in fundamental studies in fields such as microfluidics (5) and nanotechnology (6).…”

mentioning

confidence: 99%

Making polymeric micro- and nanoparticles of complex shapes

Champion

Katare

Mitragotri³

2007

682

580

Polymeric micro-and nanoparticles play a central role in varied applications such as drug delivery, medical imaging, and advanced materials, as well as in fundamental studies in fields such as microfluidics and nanotechnology. Functional behavior of polymeric particles in these fields is strongly influenced by their shape. However, the availability of precisely shaped polymeric particles has been a major bottleneck in understanding and capitalizing on the role of shape in particle function. Here we report a method that directly addresses this need. Our method uses routine laboratory chemicals and equipment to make particles with >20 distinct shapes and characteristic features ranging in size from 60 nm to 30 m. This method offers independent control over important particle properties such as size and shape, which is crucial to the development of nonspherical particles both as tools and products for a variety of fields.morphology ͉ nanotechnology ͉ geometry ͉ drug delivery ͉ nonspherical P olymeric particles are used in a diverse array of applications including drug delivery (1), advanced materials (2), personal care (3), and medical imaging (4). They also are used in fundamental studies in fields such as microfluidics (5) and nanotechnology (6). Particle shape is a critical parameter that can significantly influence particle function. The vast potential of shape, however, has not been fully explored due to difficulties in creating polymer particles with controlled shapes. Several reports exist on fabrication of polymeric particles with nonspherical geometries. These approaches make use of self-assembly (7-9), photolithography (10), nonwetting template molding (11), microfluidics (12, 13), and stretching of spherical particles (14,15). Collectively, these methods have produced particles of several distinct shapes. Some of these methods provide advantages such as scalability, high throughput, and precise control over particle shape. However, they also suffer from drawbacks including cost, particle size limitations, low throughput, and limited ability to sculpt particles in three dimensions. Accordingly, simple, versatile, inexpensive, and high-throughput methods of fabricating nonspherical particles still remain a bottleneck of future discoveries in a diverse array of fields. Here, we report a simple method that generates particles of Ͼ20 distinct shapes in large, reproducible quantities. ResultsSpherical polystyrene (PS) particles of diameters between 60 nm and 10 m are used here as a starting material for preparing particles of complex shapes. These particles are suspended in an aqueous solution of polyvinyl alcohol (PVA) and cast into films (14), which are then manipulated to engineer particle shape. The method for engineering shape can be classified into two general approaches (Fig. 1). In the first approach, termed scheme A, PS particles are liquefied by using solvent or by heating above the glass transition temperature (T g ) of PS and then stretched in one or two dimensions. In the second approach, scheme B...