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

Nanocarriers for the oral administration of therapeutic macromolecules

The main goal of this thesis has been the generation of knowledge towards the advancement of the oral administration of peptides. The specific objective has been to study how the composition and surface properties of lipid-based nanocarriers influence i) their capacity to load hydrosoluble peptides and ii) their ability to overcome the biological barriers associated to the oral modality of administration. Throughout this study, we developed a novel mixed nanosystem (nanoemulsion co-existing with micelles) able to load hydrophobically-modified insulin with a 100 % association efficiency. In brief, this nanosystem showed a great stability and miscibility in bio-relevant media, acceptable mucodiffusive properties and ability to interact and enter the intestinal cells, without relevant cytotoxic effects. Interestingly, the promising in vitro behavior of this insulin-loaded nanosystem was translated into a moderate hypoglycemic response (≈ 20−30 %) following intestinal administration to rats