Preparation of lecithin microcapsules by a dilution method using the Wurster process for intraarterial administration...

Lecithin microcapsules containing gadolinium (Gd) were designed and prepared as a dosage form for intraarterial administration to accumulate Gd in tumors in neutron capture therapy. The microcapsules were composed of 1) a lactose 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 different compositions. A dilution method using the Wurster process was developed for small-scale preparation. In spite of using only 2 g of Gd-DTPA-SAm each, three types of microcapsules were obtained with a content of 24.9% as Gd-DTPA-SAm (3.66% as Gd) even at 150% coating level. The swelling type of microcapsules (MC-D1) did not release Gd at all for the entire 120 min of the experiment in a 0.9% saline solution. On the other hand, the rapid-erosion type (MC-D2) and the vesicle-dispersing type (MC-D3) released Gd with a lag time. The percent released depended on the coating level and the SL content in the Gd-fixing layer. A large number of droplet-like particles spouted out, and/or tubular vesicles formed with MC-D2 and MC-D3 in the saline solution. These phenomena implied that the water-insoluble Gd-DTPA-SAm would be entrapped in these particles/vesicles. When MC-D2 and MC-D3 were administered to normal rats via the hepatic artery, a Gd-accumulation as high as 70 and 71% of the injected dose was detected in the whole liver 2 h after administration. In addition, biochemical and histological evaluation of the liver after administration indicated that embolization of the microcapsules actually occurred in the blood vessels, and that necrosis induced by ischemia was not serious. These results suggested that administration of these microcapsules might be multiply repeated in order to accumulate the required amount of Gd in tumors.