Protein Encapsulation Using Complex Coacervates: What Nature Has to Teach Us

Abstract

Protein encapsulation is a growing area of interest, particularly in the fields of food science and medicine. The sequestration of protein cargoes has been achieved using a variety of methods, each with benefits and drawbacks. One of the most significant challenges associated with protein encapsulation has been achieving high loading while maintaining protein viability. This difficulty has been exacerbated because many encapsulant systems require the use of organic solvents. In contrast, nature has optimized strategies to compartmentalize and protect proteins inside the cell-a purely aqueous environment. Although the mechanisms whereby aspects of the cytosol is able to stabilize proteins are unknown, the crowded nature of many newly discovered, liquid phase separated 'membraneless organelles' that achieve protein compartmentalization suggests that the material environment surrounding the protein may be critical in determining stability. Here, we focus on encapsulation strategies based on liquid-liquid phase separation, and complex coacervation in particular, which has many of the key features of the cytoplasm as a material. We review the literature on protein encapsulation via coacervation and discuss the parameters relevant to creating protein-containing coacervate formulations. Additionally, we highlight potential opportunities associated with the creation of tailored materials to better facilitate protein encapsulation and stabilization.

On Complex Coacervate Core Micelles: Structure-Function Perspectives

“…We focus in particular on the functional aspects of this novel class of adaptive, polymeric materials and highlight how structure-function relations may serve as guidelines for their rational design and development. The interested reader is referred to excellent reviews on the fundamentals and theory of these polymeric association colloids, which are briefly discussed but not addressed in-depth herein [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”

Thermostabilization of viruses via complex coacervation

“…Complex coacervation is an associative liquid-liquid phase separation phenomena that results from the electrostatic and entropic interactions between oppositely charged macro-ions. [21][22][23][24] Complex coacervation has a strong history of use as a method of encapsulation in the food and personal care industries, [25][26][27][28][29][30] and has gained recent attention for use in the fields of drug delivery [31][32][33][34][35] and gene therapy. [36][37][38] A number of reports have focused specifically on the incorporation of proteins into complex coacervates, with a goal of protecting proteins against degradation 39,40 and potentially enhancing protein thermal stability.…”

Poly(α-l-lysine)-based nanomaterials for versatile biomedical applications: Current advances and perspectives

“…The protein molecules can be encapsulated into PIC micelles with high loading efficiency under mild conditions, which prevents the use of organic solvents. The entrapped protein molecules can be well protected from rapid degradation and excretion in vivo [ [213] , [214] , [215] ]. PLLs are positively charged at physiological pH and thus can encapsulate protein molecules with negative charges in aqueous conditions by forming PIC micelles via electrostatic interactions.…”