Three-Dimensional-Printed Vortex Tube Reactor for Continuous Flow Synthesis of Polyglycolic Acid Nanoparticles with High Productivity

Abstract

Polyglycolic acid (PGA) nanoparticles show promise in biomedical applications due to their exceptional biocompatibility and biodegradability. These nanoparticles can be readily modified, facilitating targeted drug delivery and promoting specific interactions with diseased tissues or cells, including imaging agents and theranostic approaches. Their potential to advance precision medicine and personalized treatments is evident. However, conventional methods such as emulsification solvent evaporation via batch synthesis or tubular reactors via flow chemistry have limitations in terms of nanoparticle properties, productivity, and scalability. To overcome these limitations, this study focuses on the design and development of a 3D-printed vortex tube reactor for the continuous synthesis of PGA nanoparticles using flow chemistry. Computer-aided design (CAD) and the design of experiments (DoE) optimize the reactor design, and computational fluid dynamics simulations (CFD) evaluate the mixing index (MI) and Reynolds (Re) expression. The optimized reactor design was fabricated using fused deposition modeling (FDM) with polypropylene (PP) as the polymer. Dispersion experiments validate the optimization process and investigate the impact of input flow parameters. PGA nanoparticles were synthesized and characterized for size and polydispersity index (PDI). The results demonstrate the feasibility of using a 3D-printed vortex tube reactor for the continuous synthesis of PGA nanoparticles through flow chemistry and highlight the importance of reactor design in nanoparticle production. The CFD results of the optimized reactor design showed homogeneous mixing across a wide range of flow rates with increasing Reynolds expression. The residence time distribution (RTD) results confirmed that increasing the flow rate in the 3D-printed vortex tube reactor system reduced the dispersion variance in the tracer. Both experiments demonstrated improved mixing efficiency and productivity compared to traditional tubular reactors. The study also revealed that the total flow rate had a significant impact on the size and polydispersity index of the formulated PGA nanoparticle, with the optimal total flow rate at 104.46 mL/min, leading to smaller nanoparticles and a lower polydispersity index. Additionally, increasing the aqueous-to-organic volumetric ratio had a significant effect on the reduced particle size of the PGA nanoparticles. Overall, this study provides insights into the use of 3D-printed vortex tube reactors for the continuous synthesis of PGA nanoparticles and underscores the importance of reactor design and flow parameters in PGA nanoparticle formulation.

Key Fabrications of Chitosan Nanoparticles for Effective Drug Delivery Using Flow Chemistry Reactors

“… 43 The findings of this study align with those of a prior investigation that reported that increased flow rates lead to decreased residence durations, limiting the duration of nucleation and nanoparticle formation. 39 …”

“…This may be because a total flow rate that is too low or too high and not a proper chitosan and STPP mixing ratio resulted in inconsistent particle formation in the reactor, as reported previously. 39 …”

“…This factor contributes to the diminished efficacy of nanoparticle drug entrapment. 39 However, in future studies, optimizing formulation parameters and process conditions, such as adjusting the drug-to-polymer ratio and adding more mixer connections to extend the retention time, may help enhance drug entrapment efficiency.…”

“…The amount of nanoparticles produced (in milligrams) per minute was then calculated to determine the production capacities of each method. 39 …”

“…[36][37][38] In this study, chitosan nanoparticles were prepared using the flow chemistry reactor that was devised and three-dimensionally printed, as described in the previous study. 39 The operating mechanism of the reactor involved feeding two liquids into the reactor and allowing them to mix rapidly and uniformly inside the reactor, as shown in Figure 1. For this investigation, two solutions (chitosan with drug and STPP) were combined in the reactor.…”