ProDelivery · High Throughput Synthesis of Polymeric Vesicles for Protein Delivery

High Throughput Synthesis of Polymeric Vesicles for Protein Delivery

Although protein-based therapeutics have become increasingly prevalent in the clinic due to their high selectivity, their overall potency has been hampered by their instability in vivo. As a result, conventional drugs such as chemotherapeutics though generally possessing lower selectivity (and hence, more significant side effects), are still commonly employed as first line therapeutics. To improve the stability and hence potency of protein therapeutics, one approach is to develop nanoformulations encapsulating and protecting the sensitive therapeutics during delivery to the target site. The overall goal of ProDelivery has been to develop a chemical synthetic platform enabling the efficient synthesis of proteins encapsulated within polymeric nanoparticles known as polymersomes. A key aspect of the developed platform has been the optimisation of ultralow volume chemistry in order to allow for cost-efficient nanoformulation of expensive protein therapeutics. This enables greater chemical space to be explored for screening formulations and also allows a broader range of protein therapeutics to be readily accessed in the academic environment. Using the developed protein-loaded polymersome formulations, the proteins retain their activity after encapsulation, the polymersomes themselves are not cytotoxic over a broad range of concentrations and the polymersome membrane can protect the encapsulated cargo from thermal, proteolytic and intracellular stresses over prolonged periods of time. Overall, these results establish the developed chemical platform as a highly promising proof-of-concept for the stabilisation, screening and delivery of clinically relevant protein therapeutics. The multidisciplinary nature of this highly ambitious project was strongly supported by its localisation within the world-renowned Stevens Group at Imperial College London. The diverse nature of the project required input from a number of personnel within the Group with research backgrounds across chemistry, materials science, spectroscopy and cell biology and was crucial to meeting project outcomes. Ongoing collaborations which have been established as a result of this fellowship will continue to drive this work towards future applications.

Data: CORDIS, © European Union