Mixing and flow-induced nanoprecipitation for morphology control of silk fibroin self-assembly

Matthew, Saphia A. L.; Rezwan, Refaya; Kaewchuchuen, Jirada; Perrie, Yvonne; Seib, F. Philipp

doi:10.1039/d1ra07764c

Cited by 8 publications

(11 citation statements)

References 56 publications

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“…In conjunction, the production throughput could be increased by raising the flow rate of the silk precursor addition to the antisolvent in the semi-batch format and by increasing the total flow rate in the microfluidic format. In both formats, increasing the flow rates can increase silk nucleation and self-assembly [ 14 , 43 ] and would likely require the tuning of other key formulation and process parameters, such as the silk precursor:antisolvent ratio, mixing time, and shear rate of mixing.…”

Section: Discussionmentioning

confidence: 99%

“…Yield and crystallinity were analyzed across three nanoparticle batches for all participants. Data from participants 2 [ 43 ], 3 [ 14 ], and 4 [ 15 ] were published previously.…”

Section: Figurementioning

confidence: 99%

“…The remaining contents were evaluated using the Brown–Forsythe and Welch ANOVA tests. Data (±SD, n = 3) obtained from semi-batch manufacture at the 6-mL scale and the stirred 36-mL scale [ 30 ], silk II controls [ 30 ], and from participant 2 in the microfluidic format [ 43 ] were published elsewhere. Multiple groups of a silk precursor extruded with varying volume (±SD, n = 9) were evaluated by the Brown–Forsythe and Welch ANOVA against the negative silk II control (air-dried film) followed by the Dunnett T3 multiple comparison post hoc test.…”

Section: Figurementioning

confidence: 99%

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Volumetric Scalability of Microfluidic and Semi-Batch Silk Nanoprecipitation Methods

et al. 2022

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Silk fibroin nanoprecipitation by organic desolvation in semi-batch and microfluidic formats provides promising bottom-up routes for manufacturing narrow polydispersity, spherical silk nanoparticles. The translation of silk nanoparticle production to pilot, clinical, and industrial scales can be aided through insight into the property drifts incited by nanoprecipitation scale-up and the identification of critical process parameters to maintain throughout scaling. Here, we report the reproducibility of silk nanoprecipitation on volumetric scale-up in low-shear, semi-batch systems and estimate the reproducibility of chip parallelization for volumetric scale-up in a high shear, staggered herringbone micromixer. We showed that silk precursor feeds processed in an unstirred semi-batch system (mixing time > 120 s) displayed significant changes in the nanoparticle physicochemical and crystalline properties following a 12-fold increase in volumetric scale between 1.8 and 21.9 mL while the physicochemical properties stayed constant following a further 6-fold increase in scale to 138 mL. The nanoparticle physicochemical properties showed greater reproducibility after a 6-fold volumetric scale-up when using lower mixing times of greater similarity (8.4 s and 29.4 s) with active stirring at 400 rpm, indicating that the bulk mixing time and average shear rate should be maintained during volumetric scale-up. Conversely, microfluidic manufacture showed high between-batch repeatability and between-chip reproducibility across four participants and microfluidic chips, thereby strengthening chip parallelization as a production strategy for silk nanoparticles at pilot, clinical, and industrial scales.

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Section: Discussionmentioning

confidence: 99%

“…Yield and crystallinity were analyzed across three nanoparticle batches for all participants. Data from participants 2 [ 43 ], 3 [ 14 ], and 4 [ 15 ] were published previously.…”

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Volumetric Scalability of Microfluidic and Semi-Batch Silk Nanoprecipitation Methods

et al. 2022

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“…On the other hand, the “bottom-up” approaches are based on the self-assembly of the proteins from the regenerated silk fibroin (SF) aqueous solution [ 8 , 9 ], the water-in-oil emulsion solvent evaporation [ 10 ], lipid templating [ 11 ], laminar jet breakup [ 12 ], spray drying [ 13 ], two-phase microfluidic flow-focusing devices [ 14 ], self-assembly from regenerated silk fibroin ionic liquid solution [ 15 ] or via solution-enhanced dispersion by supercritical CO 2 [ 16 ]. The interest in microfluidic methods has recently increased [ 17 , 18 , 19 ] due to the homogeneity and reproducibility of the particle sizes compared to traditional methods based on precipitation in hydro-alcoholic solvents [ 9 , 20 ]. However, scaling up microfluidic-based methodology is still complex.…”

Section: Introductionmentioning

confidence: 99%

“…However, scaling up microfluidic-based methodology is still complex. Compared to the conventional bulk method, the currently purposed SFN production method is in a continuous manner, with significantly reduced size and batch-to-batch variation, which are critical factors for potential clinical translation [ 17 ]. Additionally, the method based on the precipitation of dialyzed aqueous solutions of fibroin is time-consuming and requires large volumes of water to remove the necessary salts for the dissolution of natural silk fibers.…”

Section: Introductionmentioning

confidence: 99%

Optimizing the Preparation of Silk Fibroin Nanoparticles and Their Loading with Polyphenols: Towards a More Efficient Anti-Inflammatory Effect on Macrophages

Ruiz–Alcaraz

Núñez‐Sánchez

Ruiz³

et al. 2023

Pharmaceutics

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Silk fibroin nanoparticles (SFN) have become a promising tool in drug delivery systems due to their physicochemical characteristics. SFN have shown their outstanding properties as an active vehicle for polyphenols, enhancing their antioxidant and anti-inflammatory effects on macrophages; therefore, it becomes necessary to have an easy, reproducible and scalable production method. In order to improve the production of nanoparticles, we performed direct precipitation of non-dialyzed silk fibroin solutions and evaluated the reproducibility of the method using dynamic light scattering. We also studied the loading efficiency of three different natural polyphenols using propylene glycol as a solvent. The loaded nanoparticles were fully characterized and used to treat human macrophage cells to assess the anti-inflammatory activity of these nanoparticles. The measured hydrodynamic characteristics of the SFN and the overall yield of the process showed that the new preparation method is highly reproducible and repeatable. Thus, we not only present a new scalable method to prepare silk nanoparticles but also how to improve the loading of natural polyphenolic compounds to the SFN, as well as the important anti-inflammatory effects of these loaded nanoparticles in a cell model of human macrophage cells.

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The Dawning Era of Anticancer Nanomedicines: From First Principles to Application of Silk Nanoparticles

Matthew,

Seib

2024

Advanced Therapeutics

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This review introduces nanomedicines and medical silks by addressing seminal and recent research within these fields. First, the successes of nanoparticles in improving the safety profiles and pharmacokinetic–pharmacodynamic properties are explored but also the concepts of threshold dosing and targeting of tumor‐associated macrophages. Current barriers to systemic delivery of nanomedicines are detailed and methods to overcome these barriers and increase tumor targeting are evaluated, namely: tuning the nanomedicine size and surface charge for enhanced tumor accumulation and penetration; non‐spherical nanomedicine morphologies for macrophage evasion and targeted delivery to endothelial cells; and, surface functionalization for stealth coatings and targeting receptor‐mediated endocytosis. The advantages of using silk as a nanomedicine with reference to its structure, composition, biological performance, and formulation are discussed. While batch methods for silk processing enable the formation of nano to microparticles, continuous technology can overcome bottlenecks of the deployed engineering methods such as low throughput and poor reproducibility. Finally, the chemical modification of silk using homogeneous and heterogenous chemistries is assessed within the nanomedicine context. Overall, this review covers silk nanomedicines from first principles to carrier design and on to areas of future development.

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Mixing and flow-induced nanoprecipitation for morphology control of silk fibroin self-assembly

Abstract: Tuning silk fibroin nanoparticle morphology using nanoprecipitation for bottom-up manufacture is an unexplored field that has the potential to improve particle performance characteristics.

Cited by 8 publications

References 56 publications

Volumetric Scalability of Microfluidic and Semi-Batch Silk Nanoprecipitation Methods

Volumetric Scalability of Microfluidic and Semi-Batch Silk Nanoprecipitation Methods

Optimizing the Preparation of Silk Fibroin Nanoparticles and Their Loading with Polyphenols: Towards a More Efficient Anti-Inflammatory Effect on Macrophages

The Dawning Era of Anticancer Nanomedicines: From First Principles to Application of Silk Nanoparticles

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