Advances on the formulation of proteins using nanotechnologies

This is the accepted manuscript of the following article: Santalices, I., Gonella, A., Torres, D., & Alonso, M. (2017). Advances on the formulation of proteins using nanotechnologies. Journal Of Drug Delivery Science And Technology, 42, 155-180. doi: 10.1016/j.jddst.2017.06.018Therapeutic proteins and peptides are very attractive from the pharmaceutical point of view due to their high potency and selectivity. Nonetheless, their instability and low bioavailability make their adminis- tration through non parenteral routes very difficult, a fact that hampers their efficient exploitation in therapeutics. Since the 70's, significant amount of research in the area of drug delivery and nanotech- nology has been done with the final goal of overcoming those hurdles. In particular, biodegradable and biocompatible lipid and polymer-based nanocarriers have emerged as promising delivery platforms to enable the administration of proteins and peptides. This review provides an overview of the mostly explored nanotechnologies to date intended to produce lipidic and polymeric nanocarriers for protein/ peptide delivery. The basic principles of the different techniques are discussed, and the main factors involved in the drug association and release, are analyzed. Finally, a brief overview of the potential applications of these protein/peptide-loaded nanocarriers, highlighting the nanomedicines that have reached the market or the clinical development phase, is providedS