Moving Liposome Technology from the Bench to the Oncological Patient: Towards Performance-by-Design

A liposome is defined as a spherical vesicle having multiple or a single lipid bilayer surrounding an aqueous compartment enabling the entrapment of hydrophobic or water-soluble substances respectively, and thus suitable as a drug delivery system. Different methods for preparation of liposomes at small scale were developed throughout time, establishing the principles for the introduction of modern large scale industrial production processes. Associated with the adaptation and/or introduction of powerful characterization techniques, such as dynamic light scattering for particle size distribution analysis, novel therapeutic drug delivery systems were developed aiming at the oncology setting, many reaching the clinics, such as Doxil/Caelyx (liposomal PEGylated doxorubicin). Nevertheless, the approval of novel liposome-based medicines has not fulfilled the expectations, owing to the biological barriers they face, before reaching the cancer cell in the tumor microenvironment. Accordingly, the increased understanding on cancer biology, subsequently shaping the design of the delivery system, has become paramount for the successful development of novel generations of liposomes. Thus, herein we will address the technological accomplishments associated with the development of nanoliposomal formulations, focusing on their preparation and characterization as part of the design and quality control. We will further address the impact of liposome properties on their interaction with living organisms, upon systemic administration, and how this knowledge has benefited the oncological patient.