Automated and Continuous Production of Polymeric Nanoparticles

Abstract

Polymeric nanoparticles (NPs) are increasingly used as therapeutics, diagnostics, and building blocks in (bio)materials science. Current barriers to translation are limited control over NP physicochemical properties and robust scale-up of their production. Flow-based devices have emerged for controlled production of polymeric NPs, both for rapid formulation screening (∼µg min −1) and on-scale production (∼mg min −1). While flow-based devices have improved NP production compared to traditional batch processes, automated processes are desired for robust NP production at scale. Therefore, we engineered an automated coaxial jet mixer (CJM), which controlled the mixing of an organic stream containing block copolymer and an aqueous stream, for the continuous nanoprecipitation of polymeric NPs. The CJM was operated stably under computer control for up to 24 h and automated control over the flow conditions tuned poly(ethylene glycol)-block-polylactide (PEG 5K-b-PLA 20K) NP size between ≈56 nm and ≈79 nm. In addition, the automated CJM enabled production of NPs of similar size (D h ≈ 50 nm) from chemically diverse block copolymers, PEG 5K-b-PLA 20K , PEG-block-poly(lactide-co-glycolide) (PEG 5K-b-PLGA 20K), and PEG-block-polycaprolactone (PEG 5K-b-PCL 20K), by tuning the flow conditions for each block copolymer. Further, the automated CJM was used to produce model nanotherapeutics in a reproducible manner without user intervention. Finally, NPs produced with the automated CJM were used to scale the formation of injectable polymer-nanoparticle (PNP) hydrogels, without modifying the mechanical properties of the PNP gel. In conclusion, the automated CJM enabled stable, tunable, and continuous production of polymeric NPs, which are needed for the scale-up and translation of this important class of biomaterials.

High Throughput Preparation of Poly(Lactic-Co-Glycolic Acid) Nanoparticles Using Fiber Fluidic Reactor

“…For example, the 53 g/day scale mentioned above could readily scale to 625 g/day, by utilizing a reactor of 5-cm nominal diameter instead of the 1-cm diameter utilized in this study. Similar production capacity has been reported for on-scale nanoprecipitation of amphiphilic block copolymers, including those with PLGA blocks, using novel automated coaxial jet mixer systems [33]. In comparison, laboratory scale batch processes typically result in the preparation of 1-100 mg of NPs per batch [22,34], and microfluidic systems produce NPs in the order of a few mg per hour [35].…”

Solvent Controls Nanoparticle Size during Nanoprecipitation by Limiting Block Copolymer Assembly

“…To study the combined effects of mixing kinetics and ϕ c on NP size, we used a coaxial jet mixer (CJM) to nanoprecipitate block copolymer solutions under flow. , In the CJM, a central stream containing the water-miscible solvent and block copolymer was mixed with an outer stream of water (Figure a). The flow conditions in the CJM were varied to tune Re , and thereby τ mix in the mixing channel. ,, …”

Highly Emitting Perovskite Nanocrystals with 2-Year Stability in Water through an Automated Polymer Encapsulation for Bioimaging

“…Improving the stability of perovskite NCs in water could also boost their practical application in, for example, electrocatalysis, light emitting diodes (LEDs), lasing, and inks for printable electronic devices. In parallel, the development of automated procedures that enable the rapid fabrication of perovskites NCs in water is crucial for both screening purposes and for scaling up their production, as demonstrated in other systems, − including the robust preparation of NCs/polymer nanobeads where small reaction volumes are needed. , Compared to bench protocols, such routines are also more cost-effective since less time and less manual lab work are required.…”