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

Abstract

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

Preparation and characterization of gadolinium-loaded PLGA particles surface modified with RGDS for the detection of thrombus

“…The negative zeta potential of the Gd-PLGA particles is consistent with other reported work. 15,21 The positive zeta potential of the Gd-PLGA/CS and Gd-PLGA/CS-RGDS particles and the translucent film around the particles revealed the presence of CS or CS-RGDS film on the surface of the PLGA particles, which is consistent with an earlier study. 21 A previous study suggested that the electrostatic force or ligand-receptor interactions between the positive zeta potentials of PLGA/CS or PLGA/CS-RGDS particles and the components of blood clots, such as fibrin substrates or GP IIb/IIIa receptors of the platelet membranes, would be a main factor driving the particles to permeate intrablood clots and release the loaded drugs.…”

“…As a result, the encapsulation efficiency of Gd-DTPA decreased significantly. Doiron et al 15 confirmed that Gd-DTPA appears to suffer a burst release in the first 1 hour due to the hydrophilic nature of the Gd-DTPA solution, and in their experiments, more than 90% of the Gd-DTPA solution was released within 1 hour and was almost completely released within 5 hours. During the construction of the thrombus targeted MR molecular probes, the RGDS peptide bonding procedure would take more than 2-3 hours.…”

“…Thus, the W/O/W method could be used to prepare Gd-PLGA particles, and this was confirmed by previous studies. 15,16,18,19,28 We can control the sizes of the particles and achieve their optimal characteristics by changing the parameters of the preparation procedure. 29 Accordingly, we believe that the W/O/W method is easy to perform, and the preparation procedure is simple when compared with other methods.…”

“…The size of the particles was slightly larger with the CS-RGDS film coating. Thirdly, many previous studies have reported on the release profile of the Gd-PLGA particles, 15,18 so we did not replicate the research to determine the in vitro release because we presume that the CS-RGDS film would not affect the release of Gd-DTPA and because drug release characterization in vitro correlates poorly with in vivo release. Accordingly, drug release will be characterized by our in vivo experiment in future studies.…”

“…These preparations have been confirmed to have low biological toxicity via the study of their physical and chemical characteristics, and distribution and degradation in vivo in animal models. [15][16][17] They can be imaged using 1.5 T MR scanners, and their imaging capabilities have been demonstrated to be similar to those associated with the separate use of Gd-DTPA or superparamagnetic iron oxide. Faranesh et al 18 reported that vascular endothelial growth factor (VEGF) and Gd-DTPA were encapsulated into PLGA particles in the preparation of a multifunctional contrast agent which was intended to allow the simultaneous detection and treatment of ischemic disease.…”