| 摘要 |
Compounds and methods are disclosed for directed delivery of antineoplastic drugs to the lymphatic system, which often harbors metastatic disease that is difficult to treat with conventional chemotherapy. The antineoplastic drugs form salts with lymphangitic substances, such as lymphangitic dyes, which are chemotrophic for lymphatic vessels. In particular embodiments, antineoplastic hydrazones, such as 4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007), form multiple salts (such as double salts) and complexes with heterocyclic and polyaromatic amines and sulfonic acid dyes, such as methylene blue (MB) and gentian violet (GV). The cytotoxic properties of the hydrazone compounds are potentiated by a log-fold increase in activity when the molecule is bound through electrostatic bonds to lymphangitic dyes. Directed delivery of the drugs to the lymphatic system helps treat micrometastatic disease that is present in the lymphatic system. The lymphangitic salts can be administered either systemically or locally. Local administration can include topical and intradermal administration in a solvent that promotes movement of the drug complex through the dermis and into the lymphatic vessels. |
