Preparation of lecithin microcapsules by a dilution method using the Wurster process for intraarterial administration in gadolinium neutron capture therapy

Lecithin microcapsules containing gadolinium (Gd) were designed and prepare d as a dosage form for intraarterial administration to accumulate Gd in tum ors in neutron capture therapy. The microcapsules were composed of 1) a lac tose core, 2) a layer of distearylamide of gadopentetic acid (Gd-DTPA-SAm) and polyvinylpyrrolidone (PVP) with or without soybean lecithin (SL) and 3) a membrane containing SL, cholesterol, stearic acid and PVP at three diffe rent compositions. A dilution method using the Wurster process was develope d for small-scale preparation. In spite of using only 2 g of Gd-DTPA-SAm ea ch, three types of microcapsules were obtained with a content of 24.9% as G d-DTPA-SAm (3.66% as Gd) even at 150% coating level. The swelling type of m icrocapsules (MC-D1) did not release Gd at all for the entire 120 min of th e experiment in a 0.9% saline solution. On the other hand, the rapid-erosio n type (MC-D2) and the vesicle-dispersing type (MC-D3) released Gd with a l ag time. The percent released depended on the coating level and the SL cont ent in the Gd-fixing layer. A large number of droplet-like particles spoute d out, and/or tubular vesicles formed with MC-D2 and MC-D3 in the saline so lution. These phenomena implied that the water-insoluble Gd-DTPA-SAm would be entrapped in these particles/vesicles, When MC-D2 and MC-D3 were adminis tered to normal rats via the hepatic artery, a Gd-accumulation as high as 7 0 and 71% of the injected dose was detected in the whole liver 2 h after ad ministration. In addition, biochemical and histological evaluation of the l iver after administration indicated that embolization of the microcapsules actually occurred in the blood vessels, and that necrosis induced by ischem ia was not serious. These results suggested that administration of these mi crocapsules might be multiply repeated in order to accumulate the required amount of Gd in tumors.