Preparation of Gadopentetic Acid-Loaded Chitosan Microparticles for Gadolinium Neutron-Capture Therapy of Cancer by a Novel Emulsion-Droplet Coalescence Technique

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Biodegradable gadopentetic acid (Gd-DTPA)-loaded chitosan microparticles (Gd-μCPs) were prepared as a device for gadolinium neutron-capture therapy (Gd-NCT) by a novel emulsion-droplet coalescence technique : a water-oil (w/o) emulsion A containing chitosan and Gd-DTPA in droplets and a w/o emulsion B containing NaOH in droplets were mixed and stirred to solidify chitosan as a result of collision and coalescence between droplets of each emulsion. Gd-μCPs prepared by using 100% deacetylated chitosan in 25% Gd-DTPA solution were 4.1 μm (non-lyophilized) and 3.3 μm (lyophilized) in mass median diameter, and were 3.4% in gadolinium content, corresponding to 11.7% as Gd-DTPA. The particle size and gadolinium content of Gd-μCPs were not affected by Gd-DTPA concentration in the chitosan medium. However, the deacetylation degree of chitosan influenced the particle size; as the deacetylation degree of chitosan decreased, the particle size increased. The incorporated Gd-DTPA was not released entirely from Gd-μCPs in an isotonic phosphate buffered saline solution despite the high water-solubility of Gd-DTPA (less than 0.8% with every type of Gd-μCPs). These results indicated that ion-complex formation might be contributable to incorporation of Gd-DTPA. As a preliminary study, it was confirmed that the loss of γ-ray emission by gadolinium-loading in microparticle was negligible in the thermal neutron irradiation test in vitro. These results suggested that Gd-μCPs could be usefle device for intratumoral injection into solid tumor on Gd-NCT.
公益社団法人日本薬学会の論文
1999-06-15

Preparation of Gadopentetic Acid-Loaded Chitosan Microparticles for Gadolinium Neutron-Capture Therapy of Cancer by a Novel Emulsion-Droplet Coalescence Technique

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