Coacervates: Recent developments as nanostructure delivery platforms for therapeutic biomolecules

Coacervation is a liquid–liquid phase separation that can occur in solutions of macromolecules through self-assembly or electrostatic interactions. Recently, coacervates composed of biocompatible macromolecules have been actively investigated as nanostructure platforms to encapsulate and deliver biomolecules such as proteins, RNAs, and DNAs. One particular advantage of coacervates is that they are derived from aqueous solutions, unlike other nanoparticle delivery systems that often require organic solvents. In addition, coacervates achieve high loading while maintaining the viability of the cargo material. Here, we review recent developments in the applications of coacervates and their limitations in the delivery of therapeutic biomolecules. Important factors for coacervation include molecular structures of the polyelectrolytes, mixing ratio, the concentration of polyelectrolytes, and reaction conditions such as ionic strength, pH, and temperature. Various compositions of coacervates have been shown to deliver biomolecules in vitro and in vivo with encouraging activities. However, major hurdles remain for the systemic route of administration other than topical or local delivery. The scale-up of manufacturing methods suitable for preclinical and clinical evaluations remains to be addressed. We conclude with a few research directions to overcome current challenges, which may lead to successful translation into the clinic.