Tissue distribution following subcutaneous injection of liposomes containing melphalan (MPL) was studied in rats using 14C-MPL and 3H-phosphatidylcholine. Two types of liposomes, prepared by either a brief or a prolonged sonication, were compared. Brief sonication formed large liposomes of various sizes, while liposomes obtained after a prolonged sonication were small and relatively uniform in size (34 nm in mean diameter). Subcutaneous injection of small liposomes produced a strikingly high and sustained concentration of MPL equivalents in regional lymph nodes. In contrast, most liposomes prepared by a brief sonication appeared to remain at the injection site, and there was only a slight increase in the lymph node concentration of MPL equivalents over the plasma level during the 24-hour experiments.
Effects of maleic anhydride-divinyl ether (MVE-2) on lymph node and lung metastases were studied in rats transplanted with a syngeneic mammary adenocarcinoma. Subcutaneous treatment with MVE-2 was administered according to various schedules, with or without surgical removal of the primary tumor. A significant reduction in size and/or incidence of lymph node metastases was observed, although no effect on the primary tumor was noted. Histologic evidence of degeneration of metastatic tumor cells, which were surrounded by lymphocytes and a characteristic focal histiocytosis, was present in the regional lymph nodes. The number of lung metastases resulting from iv injection of tumor cells was also significantly reduced following iv injection of MVE-2.
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