Preparation of gadopentetic acid-loaded chitosan microparticles for gadolinium neutron-capture therapy of cancer by a novel emulsion-droplet coalescence technique.
Biodegradable gadopentetic acid (Gd-DTPA)-loaded chitosan microparticles (Gd-microCPs) were prepared as a device for gadolinium neutron-capture therapy (Gd-NCT) by a novel emulsion-droplet coalescence technique: a water-in-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-microCPs prepared by using 100% deacetylated chitosan in 25% Gd-DTPA solution were 4.1 microns (non-lyophilized) and 3.3 microns (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-microCPs 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-microCPs in an isotonic phosphate buffered saline solution despite the high water-solubility of Gd-DTPA (less than 0.8% with every type of Gd-microCPs). 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 gamma-ray emission by gadolinium-loading in microparticle was negligible in the thermal neutron irradiation test in vitro. These results suggested that Gd-microCPs could be a useful device for intratumoral injection into solid tumor on Gd-NCT.
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
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Tokumitsu
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Ichikawa
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Fukumori
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D002240:Carbohydrate Sequence; D002686:Chitin / Q000031:analogs & derivatives; D048271:Chitosan; D003287:Contrast Media / Q000737:chemistry*; D003640:Dealkylation; D004655:Emulsions; D005682:Gadolinium / Q000032:analysis / Q000737:chemistry*; D019786:Gadolinium DTPA / Q000737:chemistry*; D005720:Gamma Rays; D008863:Microspheres; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000532:radiotherapy*; D017247:Neutron Capture Therapy; D010316:Particle Size; D011868:Radioisotopes
D003287:Contrast Media; D004655:Emulsions; D011868:Radioisotopes; D002686:Chitin; D048271:Chitosan; D005682:Gadolinium; D019786:Gadolinium DTPA