Doxil® — The First FDA-Approved Nano-Drug: From an Idea to a Product

Abstract

Doxorubicin in liposomes (abbreviated and registered as Doxil) is an anticancer nano-drug. Doxil is based on three unrelated principles: (T) using sterically stabilized liposomes, steric stabilization being achieved by the presence of pegylated distearoyl phosphatidylethanolamine (2000Da PEG-DSPE), which results in long blood circulation time of the liposomes; pi] high and stable remote loading of doxorubicin driven by a transmembrane ammonium sulfate gradient, which also allows for drug release at the tumor; and (iii) having the liposome lipid bilayer in the "liquid ordered" phase based on the high-Tm (53°C) hydrogenated soy phosphatidylcholine, and on cholesterol. In order to take advantage of the enhanced permeability and retention (EPR) effect and to achieve passive targeting of the liposomes into the tumor, the liposomes are nanoscale. 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