Chapter Three - Lipid nanoparticle steric stabilization roadmap

Lipid nanoparticles, such as liposomes, cubosomes, hexosomes, solid lipid nanoparticles and nanostructured lipid carriers, have grown in popularity in many biomedical applications including vaccine and nanomedicine development in the last few years. These systems generally require steric stabilizers to maintain colloidal stability in an aqueous medium, as well as to improve in vivo pharmacokinetics and biodistribution profiles. To date, polyethylene glycol (PEG)-lipid conjugates and block copolymers such as Pluronic® F127 are the most commonly employed stabilizers in these systems due to their commercial availability, excellent ability to stabilize the lipid nanoparticles, and the in vivo “stealth” benefit of PEGylated particle surfaces for prolonged blood circulation. However, in recent years, concerns about the immunogenicity and the impeded cell interaction of nanoparticles containing a PEG layer have been rising and driving research interests in designing alternative steric stabilizers, with additional functionalities such as stimuli-responsiveness. This chapter summarizes the classes of steric stabilizers used in lipid nanoparticle formulations, discusses the latest development of custom-designed novel steric stabilizers, identifies current knowledge gaps in steric stabilizer design principles and selection criteria, and presents a development roadmap for next-generation steric stabilizers as a key functional component of lipid nanoparticles.