ABSTRACT
This chapter describes the downs and ups of pre-Doxil and Doxil formulations, and how the lessons learned from the failure of pre-Doxil liposomal doxorubicin formulations were turned into the Doxil success. It demonstrates that such a development requires a multidisciplinary approach and is highly dependent on understanding and optimal use of physicochemical and nanotechnology principles. Liposomes were proposed as a good option for a drug delivery system by Alec Bangham already in the 1960s, soon after he described liposomes as an excellent model system for biological membranes in 1964. Most liposomal doxorubicin formulations developed during the 1980s took advantage of doxorubicin’s being an amphipathic weak base that can associate efficiently with negatively charged membrane lipids. For liposome formulation designed for metastatic tumor treatment, intravenous administration is the only option, and therefore high loading level and its high stability during storage and blood circulation are required.
