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.