2024 AIChE Annual Meeting
Optimized Co-Encapsulation of Colloidal Nanocrystals and Small Molecules into Polymeric Nanoparticles Via Sequential Nanoprecipitation (SNaP)
Polymeric core-shell nanoparticles (NPs) are widely used as effective carriers for active pharmaceutical ingredients (API) in various biomedical applications. The formation of NPs carrying colloidal materials, including iron oxide nanocrystals (IONC) and quantum dots (QD), has drawn substantial interest due to their extensive physical and optoelectronic properties as medical contrast agents. However, while the parameters that control small, hydrophobic molecule formation in NP precipitation have been thoroughly investigated, there is limited knowledge on the assembly process of colloidal materials. In this work, we encapsulate IONCs (5-20 nm) and QDs (5 nm) alongside a small molecule fluorophore into stable NPs via two different precipitation processes, Flash Nanoprecipitation (FNP) and Sequential Nanoprecipitation (SNaP), and compare their control over NP size, API loading, and cargo uniformity. FNP is a well-established, one-step process that involves the simultaneous core formation of hydrophobic molecules and adsorption of the stabilizing amphiphilic block-copolymer through rapid mixing. SNaP is an emergent synthesis process which utilizes similar mixing principles as FNP, but incorporates a two-step sequential mixing modality, creating the ability to delay the time points at which components are incorporated into the NP. Characterization of the FNP particles showed a lack of control of NP size with generic formulation variables such as percent cores and total mass concentrations. There was also notable nonuniformity in API and nanocrystal distribution among formed NPs, which was visualized using Transmission Electron Microscopy (TEM). Through SNaP, the nanocrystals aggregated prior to block-copolymer stabilization, yielding increased control over NP size, ranging from 100-250 μm in diameter, and a 2-fold improvement in API uniformity compared to FNP. These results highlight the application of SNaP as a robust, scalable method for the synthesis of multimodal nanoparticles with both drug delivery and bioimaging capabilities. Future work will continue to optimize the manufacturing processes of theranostic nanoparticles.