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  • Title: Preparation and characterization of radioactive dirhenium decacarbonyl-loaded PLLA nanoparticles for radionuclide intra-tumoral therapy.
    Author: Hamoudeh M, Salim H, Barbos D, Paunoiu C, Fessi H.
    Journal: Eur J Pharm Biopharm; 2007 Nov; 67(3):597-611. PubMed ID: 17521895.
    Abstract:
    This study describes the development of biocompatible radioactive rhenium-loaded nanoparticles for radionuclide anti-cancer therapy. To achieve this goal, dirhenium decacarbonyl [Re2(CO)10] has been encapsulated in poly(L-lactide) based nanoparticles by an oil-in-water emulsion-solvent evaporation method. A 3(3) factorial design method was applied to investigate the influence of both the proceeding and formulation parameters including the stirring speed and the concentration of both the PLLA polymer and the poly(vinyl alcohol) stabiliser on both nanoparticles size and the Re2(CO)10 encapsulation efficacy. The factorial design results attributed a clear negative effect for the stirring speed and the stabiliser concentration on the nanoparticles size while the polymer concentration exhibited a positive one. Regarding the Re2(CO)10 encapsulation efficacy, higher values were obtained when higher polymer concentrations, lower stabiliser concentrations or slower stirring speeds were applied in the preparation. Different tests were thereafter performed to characterize the Re2(CO)10-loaded nanoparticles. The nanoparticles size, being experimentally controlled by the above mentioned parameters, ranged between 330 and 1500 nm and the maximum rhenium loading was 24% by nanoparticles weight as determined by atomic emission assays and neutron activation analysis. Furthermore, the rhenium distribution within nanoparticles has been shown to be homogeneous as confirmed by the energy dispersive X-ray spectrometry. DSC assays demonstrated that Re2(CO)10 was encapsulated in its crystalline initial state. Other experiments including FT-IR and NMR did not show interactions between PLLA and Re2(CO)10. To render them radioactive, these nanoparticles have been bombarded with a neutron flux of 1.45x10(13) n/cm2/s during 1 h. The SEM micrographs of nanoparticles after neutron bombardment showed that the nanoparticles remained spherical and separated but slightly misshaped. These applied neutron activation conditions yielded a specific activity of about 32.5 GBq per gram of nanoparticles. Preliminary estimations allow us to think that a sole injection of 50 mg of these activated nanoparticles into a brain tumor model (4.2 cm diameter) would deliver a tumor absorbed dose of up to 47 Gy. In conclusion, these dirhenium decacarbonyl-loaded nanoparticles represent a novel promising tool for radionuclide anti-cancer therapy.
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