(282a) High-Throughput and Scalable Synthesis of Polyanhydride Nanoparticles Via Spray Drying

Biodegradable polyanhydride nanoparticles represent a viable platform for the delivery of vaccine antigens and small molecule drugs. These nanoparticles, comprised of copolymers of sebacic anhydride (SA), 1,6-bis(p-carboxyphenoxy)hexane (CPH), and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), sustain the release kinetics of payloads and preserve the stability of encapsulated payloads upon release. Additionally, the inherent adjuvant properties of polyanhydrides promote robust cellular and humoral immune responses, making them excellent vaccine formulations.

Polyanhydride nanoparticles are routinely synthesized via a solid-oil-oil flash nanoprecipitation process. However, this methodology generally limits the batch size to approximately 100 mg of nanoparticles. In addition, flash nanoprecipitation requires vast amounts of expensive non-solvents for nanoparticle precipitation, and must be chilled with liquid nitrogen. Finally, the flash nanoprecipitation method often results in aggregated nanoparticles, often times with inconsistent batch-to-batch variability. Thus, we sought to design a high-throughput, scalable, and cost-effective method for the synthesis of discrete polyanhydride nanoparticles with high batch-to-batch consistency. In this work, we developed a novel spray drying method for synthesizing nanoparticles using the Buchi B90 HP spray dryer. Spray dried polyanhydride nanoparticles could be achieved with high reproducibility, with yields as high as 75%, and with protein encapsulation efficiencies similar to that of the standard flash nanoprecipitation methods. The synthesized nanoparticles had diameters of approximately 600-700 nm, compared to approximately 250 nm with flash nanoprecipitation. However, the spray dried particles demonstrated discrete morphology and suspended well in solution, with improved suspension quality over flash nanoprecipitation-synthesized nanoparticle formulations. This method can be broadly applied to many different types of polymers and payloads and shows great promise as a method for rapidly producing nanoparticles with high consistency for academic research and with scalability for applications in the pharmaceutical industry.