(416d) High Throughput Synthesis of Nanovaccine Formulations

Authors: 
Goodman, J., Iowa State University
Dunshee, L., Iowa State University
Mitra, A., Iowa State University
Narasimhan, B., Iowa State University

Using nanoscale vehicles to deliver protein antigens in the development of vaccines has been a well-studied area of research. High throughput techniques utilizing combinatorial libraries have the potential to be a valuable resource in rapidly synthesizing and screening nanoscale biomaterial-based carriers for drug and vaccine delivery. In this study, we highlight the development of an automated high-throughput robot for synthesizing polyanhydride nanoparticles containing protein antigens. Polyanhydrides are a class of safe and biodegradable polymers that have been widely used as a vaccine adjuvant/carrier. The method we have developed was based on a multiplexed homogenizer and has the capacity to handle parallel streams of monomer or polymer solutions to synthesize polymers and/or nanoparticles. Copolymers were synthesized from sebacic acid (SA), 1,6-bis(p-carboxyphenoxy)hexane (CPH), and 1,8-bis(p-carboxyphenoxy)-3,6-dioxactane (CPTEG). Nanoparticles loaded with the model antigen, ovalbumin, were synthesized using anti-solvent nanoprecipitation. Concentrations of surfactant were varied to test its effect on protein encapsulation efficiency as well as protein release kinetics. We observed that surfactant concentration did not significantly affect protein release rate, but greatly enhanced protein encapsulation efficiency. Particles synthesized with the high throughput method were compared to particles made with conventional anti-solvent nanoprecipitation to validate the high throughput approach. Protein burst and release rates between the two methods were similar, even though particles synthesized using the high-throughput technique were observed to be smaller. Finally, we demonstrated that the high-throughput method could be adapted to functionalize the surface of the particles to aid in the design of targeted drug and vaccine delivery systems. Our results showed that the developed high-throughput system is a viable alternative to conventional methods for studying vaccine and drug delivery vehicles, with the potential to more rapidly optimize the design of these systems.