Synthesis of degradable particles by free radical polymerization in dispersed – CKAPART

Among the different classes of polymers, vinyl polymers are used in a wider and wider range of applications, especially as biomaterials for which the degradability and the safety of the polymer is a critical issue. The development of (bio)degradable polymers is currently the focus of great attention given their extensive use in many different areas including (nano)medicine, microelectronics and environmental protection. Taking advantage of the facile synthetic routes associated with the production of vinyl polymers, different strategies have been developed to provide the resulting polymers with degradability features. The simplest strategy is to use a degradable crosslinking agent. Although not linear, the resulting polymeric network can be degraded into smaller molar mass fragments by cleavage of the crosslinker. Other strategies can give access to degradable linear chains. They are based on condensation of small degradable molecules or oligomers. These strategies however often require multistep chemistries limiting their wide applicability. This is probably the reason why a very large number of commercially available biodegradable materials for medical and non-medical applications is based on aliphatic polyesters, for which in-chain ester bonds can be cleaved under hydrolytic conditions or in presence of specific enzymes (e.g., esterases). Polyesters are obtained by (co)polymerization of glycolide, lactide, epsilon-caprolactone and/or their corresponding derivatives. While vinyl polymers can be easily obtained as waterborne polymer suspension by a free radical process, polyesters are mainly obtained by ring-opening polymerization or polycondensation, techniques that are not easily compatible with the preparation of waterborne polymeric particles. As a result, degradable polyester particles that are of paramount importance in bio-related fields (e.g., manufacture of resorbable sutures, tissue engineering scaffolds, micro- and nanoscale drug delivery systems), but also of concern in sustainable development, are almost exclusively obtained from formulation of preformed polymers by emulsification methods (e.g., nanoprecipitation, emulsion-solvent evaporation). However, very low solids content dispersions are obtained (1-5 wt.%), which represents a major limitation in terms of use and industrial development.
Therefore, there is an unmet fundamental and industrial need for new synthetic strategies to develop degradable polyester-like particles that could circumvent the limitations of current systems in terms of process and colloidal features and advantageously replace some specific traditional latexes to yield more eco-friendly materials.
Polyesters- or in-chain ester-containing vinyl polymers can indeed be obtained via a free radical (co)polymerization of cyclic ketene acetal (CKA), a class of monomers able to undergo radical ring opening (co)polymerization (rRO(co)P). The radical nature of rROP opens the way to its transposition in dispersed media, the preferred industrial process to produce high solids content vinyl polymer particle dispersion, particularly in water. This is however associated with real challenges related to hydrolytic stability of CKAs.
The aim of the CKAPART project is to develop innovative strategies to prepare degradable vinyl copolymers in dispersed media by producing polyester-like particles. To meet this challenge, a range of new CKAs being hydrophilic, hydrophobic or functional will be synthesized and evaluated in miniemulsion or seeded emulsion polymerizations. CKAPART further wants to assess the degradability and the potential of the obtained particles dispersed in water for the formation of nanocarriers for drug delivery and imaging applications.