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 (G d-mu CPs) were prepared as a device for gadolinium neutron-capture therapy (Gd-NCT) by a novel emulsion-droplet coalescence technique: a eater-in-oil (mlo) emulsion A containing chitosan and Gd-DTPA in droplets and a w/o emul sion B containing NaOH in droplets were mixed and stirred to solidify chito san as a result of collision and coalescence between droplets of each emuls ion. Gd-mu CPs prepared by using 100% deacetylated chitosan in 25% Gd-DTPA solution were 4.1 mu m (non-lyophilized) and 3.3 mu m (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-mu CPs were n ot affected by Gd-DTPA concentration in the chitosan medium. However, the d eacetylation degree of chitosan influenced the particle size; as the deacet ylation degree of chitosan decreased, the particle size increased, The inco rporated Gd-DTPA was not released entirely from Gd-mu CPs in an isotonic ph osphate buffered saline solution despite the high water-solubility of Gd-DT PA (less than 0.8% with every type of Gd-mu CPs). These results indicated t hat ion-complex formation might be contributable to incorporation of Gd-DTP A. As a preliminary study; it was confirmed that the loss of gamma-ray emis sion by gadolinium-loading in microparticle nas negligible in the ther mal neutron irradiation test in vitro. These results suggested that Gd-mu CPs c ould he a useful device for intratumoral injection into solid tumor on Gd-N CT.