Design and applications of protein delivery systems in nanomedicine and tissue engineering

Proteins are biological macromolecules involved in a wide range of biological functions, which makes them very appealing as therapeutics agents. Indeed, compared to small molecule drugs, their endogenous nature ensures their biocompatibility and biodegradability, they can be used in a large range of applications and present a higher specificity and activity. However, they suffer from unfolding, enzymatic degradation, short half-life and poor membrane permeability. To overcome such drawbacks, the development of protein delivery systems to protect, carry and deliver them in a controlled way have emerged importantly these last years. In this review, the formulation of a wide panel of protein delivery systems either in the form of polymer or inorganic nanoengineered colloids and scaffolds are presented and the protein loading and release mechanisms are addressed. A section is also dedicated to the detection of proteins and the characterization methods of their release. Then, the main protein delivery systems developed these last three years for anticancer, tissue engineering or diabetes applications are presented, as well as the major in vivo models used to test them. The last part of this review aims at presenting the perspectives of the field such as the use of protein-rich material or the sequestration of proteins. This part will also deal with less common applications and gene therapy as an indirect method to deliver protein.