Smart polymersomes and hydrogels from polypeptide-based polymer systems through α-amino acid N-carboxyanhydride ring-opening polymerization. From chemistry to biomedical applications

The synthesis of smart stimuli-responsive polymeric materials for nanomedicine applications has attracted the interest of a large number of scientists that focuses on the effective encapsulation of pharmaceutical compounds and control of their biodistribution. The development of multifunctional polymeric materials is mainly guided by the goal of achieving active compounds which selectively target the pathological sites, therefore minimizing systemic side effects. These materials are divided in two categories based on their mode of administration: the first is based on systemic administration, while the second relies on localized mode of action. Polymersomes are nanocarriers that are delivered through the blood compartment and are the best systems to carry both hydrophilic drugs in their interior hollow space or/and hydrophobic drugs encapsulated in their hydrophobic layer. Polymeric hydrogels on the other hand are systems for localized drug delivery of both kinds of pharmaceuticals, depending on their solubility. Even though a large number of polymeric materials that form either nanocarrier or hydrogel delivery systems has been investigated, a surprisingly small subset of these technologies has demonstrated potentially curative preclinical results, and fewer have progressed towards commercialization. One of the most promising classes of polymeric materials for drug delivery applications is polypeptides, which combine the properties of the conventional polymers with the 3D structure of natural proteins such as α-helices and β-sheets. In this article, the synthetic pathways followed to develop well-defined stimuli-responsive polymer delivery systems based on polypeptides that have been prepared through ring-opening polymerization (ROP) of N-carboxyanhydrides are reviewed, including a discussion of their in vivo and in vitro efficacy. This review is limited to systems presented over the last eighteen years.