Flow‐based reactor design for the continuous production of polymeric nanoparticles

Bovone, Giovanni; Guzzi, Elia A.; Tibbitt, Mark W.

doi:10.1002/aic.16840

Cited by 21 publications

(40 citation statements)

References 60 publications

(86 reference statements)

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“…Ultrapure deionized water (dH 2 O) was freshly filtered using a Milli-Q IQ 7000 from Merck Millipore (CH). All components of the coaxial jet mixer were purchased from BGB Analytik (CH) or Cole-Parmer (US) and are listed in detail in our recent work (Bovone et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

“…The CJM design was based on similar devices used for inorganic particle synthesis and a recently developed device from our group for the flow-based production of polymeric nanoparticles (Baber et al, 2015;Bovone et al, 2019). The CJM was assembled from off-the-shelf components within minutes.…”

Section: Flow-based Nanoparticle Formationmentioning

confidence: 99%

“…The alignment of the capillary and the main channel was the most difficult step and extra care should be taken here to ensure proper alignment of the device. The effect of alignment on NP production was tested previously by disassembling and reassembling the device after each synthesis (Bovone et al, 2019). NP fabrication with different capillary alignments showed a variability of up to ±10 nm.…”

Section: Flow-based Nanoparticle Formationmentioning

confidence: 99%

“…Microfluidic devices based on hydrodynamic flow focusing have been used for formulation screening (µg min −1 ), while on-scale production (mg min −1 to g min −1 ) was achieved with impinging jet mixers and coaxial jet mixers (CJMs) (Karnik et al, 2008;Lim et al, 2014;Hickey et al, 2015;Liu et al, 2015;Rode García et al, 2018). In our recent work, we developed a CJM from off-the-shelf components for flow-based production of NPs that enabled tunable NP size in both formulation screening mode (∼µg min −1 ) and scalable production mode (∼mg min −1 ) (Bovone et al, 2019). While flow-based devices have improved the process engineering and production of polymeric NPs, automated processes are needed to offer user-independent scale-up and to minimize human intervention during pharmaceutical production.…”

Section: Introductionmentioning

confidence: 99%

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Automated and Continuous Production of Polymeric Nanoparticles

Bovone

Steiner

Guzzi

et al. 2019

Front. Bioeng. Biotechnol.

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Flow-based Nanoparticle Formationmentioning

confidence: 99%

Section: Flow-based Nanoparticle Formationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Automated and Continuous Production of Polymeric Nanoparticles

Bovone

Steiner

Guzzi

et al. 2019

Front. Bioeng. Biotechnol.

Self Cite

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“…An extensive effort is required to manufacture degradable polymer particles with defined sizes through suitable control of their production process, optimization of the mixing conditions, and increased mass transfer between the two phases [18,19]. Previous studies demonstrated that these conditions are provided by applying microfluidic devices, which improve the control of the size and size distribution of particles [17,[20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Polycaprolactone Nanoparticles through Flow‐Focusing Microfluidic‐Assisted Nanoprecipitation

Heshmatnezhad

Nazar

2020

Chem Eng & Technol

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Polycaprolactone nanoparticles (PCL NPs) were produced by a liquid nonsolvent nanoprecipitation process in a flow‐focusing microfluidic device and optimized in terms of particle size, polydispersity index (PDI), and zeta potential ζ. The effects of flow rate ratio (FRR), total flow rate (TFR), the organic solvents tetrahydrofuran and dimethylformamide (DMF), the surfactants polyvinyl alcohol and Tween 80, and polymer molecular weight on the size, PDI, and ζ of PCL NPs were investigated. A stability study was performed to compare the effect of the surfactants on the characteristics of PCL NPs over 7 d. The smallest particles are produced at the highest FRR, TFR, and polymer molecular weight and lowest polymer concentration in DMF. The presence of both surfactants results in smaller NPs.

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Microfluidic Platforms for the Production of Nanoparticles at Flow Rates Larger Than One Liter Per Hour

Giorello

Nicastro²

2022

Adv Materials Technologies

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processes, which are essential for the preparation of nanoparticles (NPs) with specific properties. A proof of acceptance of these modern drug formulation processes has been the recent FDA and EMA approval of nucleic acid nanomedicines, first Onpattro [10] and nowadays COVID-19 vaccines, [11] where microfluidics plays an essential R&D role. [12] Regarding massproduction, a limitation of the present microfluidic technology is the relatively low throughput, [13] which is insufficient to meet the good manufacturing practice (GMP) standards of the pharmaceutical industry in terms of final product volumes. Therefore, continuous efforts are being made to upscale the NPs preparation processes, and this is precisely the subject to be analyzed in the present work.Before entering the specific scaling-up problem, it is worth discussing the topic in a wider context. Up to date, nanomedicine has not reached the expected success, which can be explained by the challenges that still remain in formulation, the lack of robust and reproducible manufacturing, the highly demanded characterization methods, and stringent regulatory requirements. [14] Microfluidics has the potential to solve some of these issues and influence the way pharmaceutical R&D is conducted; [15] thus governmental agencies are now backing such initiatives, as mentioned above. It is worth mentioning that microfluidics is not a product but an enabling technology, a versatile tool that has been constantly evolving during the last two decades. [16] For example, early microfluidic components were expensive and time consuming, not only for chips fabrication but also for handling and operation. However, today there is a broad availability of microfabrication, integration, and liquid-handling methods, [17][18][19] which is quickly enlarging the number of users in both industry and academy. There are three expanding sectors producing the major demands on microfluidic technology: i) lab-on-a-chip devices for point-of-care testing, [20] ii) microfluidics-based 3D cell culture systems, such as organ-on-a-chip for precision medicine, [21] and iii) microfluidic platforms for the preparation of smart drug delivery nanosystems. [1][2][3][4] Furthermore, the combination of these applications is generating a number of novel opportunities for the biomedical market, and it is also accelerating the clinical translation of NPs, as envisioned some years ago. [22] Nevertheless, the conversion of these nanomedicine prototypes into marketed products is still limited.The pharmaceutical industry is regarded as rather conservative, a conduct that is well-understood considering the strict The convergence of microfluidics and nanotechnology has demonstrated a synergetic potential for the preparation of advanced pharmaceutics. Nowadays, there is a renewed interest in the subject, boosted by the approval of nucleic acid-loaded lipid-based nanoparticles. Microfluidics enables the physical scenario to achieve well-controlled formulations and plays an essential role in nanocarriers development; ne...

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Flow‐based reactor design for the continuous production of polymeric nanoparticles

Cited by 21 publications

References 60 publications

Automated and Continuous Production of Polymeric Nanoparticles

Automated and Continuous Production of Polymeric Nanoparticles

Synthesis of Polycaprolactone Nanoparticles through Flow‐Focusing Microfluidic‐Assisted Nanoprecipitation

Microfluidic Platforms for the Production of Nanoparticles at Flow Rates Larger Than One Liter Per Hour

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