Drug conjugates with albumin and transferrin

Transferrin and albumin are potential macromolecular carriers for improving biodistribution, pharmacokinetic profile and targeting potential of drugs in general. Although the tissue distribution of transferrin and albumin is naturally influenced by their biology and functional role, a series of investigations have shown that the anatomical and physiological characteristics of tumour tissue can serve as a 3D target and mediate the uptake of these serum proteins. This review covers the patent literature on the development of transferrin and albumin drug conjugates from 1985 onwards, with emphasis on the patent applications from the past 2 - 3 years. Initially, antitumour and antiviral agents were conjugated with both proteins and early clinical trials have been performed with transferrin conjugates of cisplatin and doxorubicin, with adenine arabinoside monophosphate conjugated to lactosaminated albumin and with methotrexate bound to albumin. New approaches have concentrated on forming a drug albumin conjugate in vivo, by selectively binding drug derivatives to circulating albumin after iv. administration. Clinical trials with an albumin-binding doxorubicin prodrug and a long acting opioid component are being initiated or are in progress.