Design of poly(HEMA) particles in supercritical carbon dioxide for protein delivery

A vast majority of the polymer nanocarriers have been designed and developed for the controlled and targeted release of hydrophobic drugs. However, there are still some challenges to design appropriate carriers for the delivery of therapeutic proteins or peptides. Although the history of the protein/peptide based drugs dates back to insulin production, they have taken great attention since the last decades due to their possible broad range of therapeutic applications. They might offer more specific and safer therapies in comparison to small molecules drugs. Nonetheless, their encapsulation remains challenging especially to preserve their specific structure and activity in the formulations. For this purpose, hydrogel particles (nano-/microgels) have emerged as promising polymer carriers for such proteins. This work focuses on the synthesis of nano-/microgels encapsulating therapeutic proteins and peptides in supercritical carbon dioxide which confers environmentally benign features to the synthesis method. More precisely, hydrogel particles were obtained by free-radical dispersion polymerisation of 2-hydroxyethyl methacrylate (HEMA) in supercritical carbon dioxide in presence of a cross-linker and a suitable stabiliser. Two kinds of stabilisers have been designed and studied, i.e. a photocleavable perfluorinated stabiliser and a fluorine-free stabiliser. The optimisation of the dispersion polymerisation conditions led to well-defined cross-linked particles. The process was robust enough to incorporate a drug or a peptide to encapsulate in one-pot synthesis into the particle network. In a subsequent step such drug loaded particles were dispersed successfully in aqueous media and shown sustained release of their content. This was demonstrated notably for the release of a bactericidal peptide.