Polyion Complex Micelles for Protein Delivery

Abstract

Proteins are ubiquitous in life and next to water, they are the most abundant compounds found in human bodies. Proteins have very specific roles in the body and depending on their function, they are for example classified as enzymes, antibodies or transport proteins. Recently, therapeutic proteins have made an impact in the drug market. However, some proteins can be subject to quick hydrolytic degradation or denaturation depending on the environment and therefore require a protective layer. A range of strategies are available to encapsulate and deliver proteins, but techniques based on polyelectrolyte complex formation stand out owing to their ease of formulation. Depending on their isoelectric point, proteins are charged and can condense with oppositely charged polymers. Using block copolymers with a neutral block and a charged block results in the formation of polyion complex (PIC) micelles when mixed with the oppositely charged protein. The neutral block stabilises the charged protein–polymer core, leading to nanoparticles. The types of micelles are also known under the names interpolyelectrolyte complex, complex coacervate core micelles, and block ionomer complexes. In this article, we discuss the formation of PIC micelles and their stability. Strategies to enhance the stability such as supercharging the protein or crosslinking the PIC micelles are discussed.

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 ].…”

Protein–Polyelectrolyte Complexes and Micellar Assemblies

“…Furthermore, proteins can be shielded from harsh conditions in the outer medium wherein loss of activity might occur, such as at high temperature or exposure to organic media. Consequently, these protein-containing structures have garnered interest both in laboratory and in vivo settings and have been employed for targeted, controlled delivery of therapeutic proteins as substitutes for PEGylation approaches [134,135].…”

Polyion Complex Micelles for Protein Delivery Benefit from Flexible Hydrophobic Spacers in the Binding Group

“…Polyion complex (PIC) micelles have been widely employed for the delivery of proteins and enzymes thanks to the mild conditions in which they can be assembled and the chemical diversity which can be incorporated. [1][2][3][4][5][6][7][8] Typically such micelles are prepared from block copolymers possessing a hydrophilic neutral block (for colloidal stability against aggregation) and a charged block which binds to the oppositely charge protein, thus incorporating it into the center of the micelle. [9][10][11][12] While PIC micelles form readily between proteins and many block copolymers, the nature of the polymer has a strong effect on the binding strength, aggregation number, and therefore the size of the micelle.…”