(143b) High Throughput Evaluation of the In Vivo Biodistribution and Dispersion of Polyanhydride Nanoparticle Adjuvants

While vaccination remains the best strategy for disease prevention, current vaccine strategies often require large doses of poorly immunogenic antigens, repeated immunizations, and undesirable side effects, which can all hinder vaccine efficacy. Furthermore, most current vaccine administration routes differ from that of the natural infection which could limit immune protection. Thus, there is a need for the development of biocompatible vaccine adjuvants capable of multi-route administration and prolonged antigen release.

Polyanhydrides are a class of biodegradable, non-toxic, non-mutagenic materials that are capable of encapsulating and delivering biological molecules in vivo. These polymers are capable of being formulated into nanoparticles enabling administration parenterally or intranasally. Nanoparticles based upon copolymers of sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy hexane) (CPH), and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaocatane) (CPTEG) have been shown to exhibit tunable properties, including tailored protein release kinetics, protein stabilization, and immunomodulatory adjuvant behavior. In this work, a combinatorial platform was utilized to investigate the in vivo biodistribution, depot effect, and mucoadhesion of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. This was achieved by employing a live animal imaging system with near infrared fluorescent markers to simultaneously investigate each parameter. All nanoparticle chemistries resulted in rapid dispersal when delivered intranasally and provided a long-term depot when administered parenterally. Chemistry-dependent trends were identified in which intranasally administered amphiphilic and hydrophobic polyanhydride nanoparticles, 50:50 CPTEG:CPH and 50:50 CPH:SA, demonstrated superior mucoadhesive properties enabling prolonged residence in lung tissue. It was observed that parenterally administered amphiphilic 50:50 CPTEG:CPH nanoparticles demonstrated the longest injection site residence time. These results provide new insights into the biodistribution and tissue-specific targeting of these nanoparticle-based vaccine adjuvants. The mucoadhesive polymer nanoparticles identified in this work provide opportunities for their use as adjuvants in intranasal and parenteral vaccination. Furthermore, the insights gained from these studies will enable the rational design of vaccine and therapeutic drug delivery systems for targeted and localized delivery over extended time periods.