Three-dimensional, symmetrically assembled microfluidic device for lipid nanoparticle production

Kimura, Niko; Maeki, Masatoshi; Sasaki, Kosuke; Sato, Yusuke; Ishida, Akihiko; Tani, Hirofumi; Harashima, Hideyoshi; Tokeshi, Manabu

doi:10.1039/d0ra08826a

Cited by 24 publications

(19 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Microfluidic Synthesis Of Organic Npsmentioning

confidence: 99%

“…[ 48 ] Similarly, comparing to the 2D‐iLiNP device, the 3D‐iLiNP device produced siRNA‐loaded lipid NPs with a more uniform size. [ 91 ]…”

Section: Microfluidic Synthesis Of Organic Npsmentioning

confidence: 99%

“…To overcome these disadvantages, microfluidic approaches have been developed to produce lipid NPs with well-controlled size and size distribution. [84] Microfluidic devices with various structures have been designed to control lipid NP formation including HFF devices, staggered herringbone micromixer, [86,87] T-shape microfluidic device, [88] 2D and 3D invasive lipid NP production (iLiNP) device (Figure 5b), [89][90][91] and glass capillary-based microfluidic-chip. [92] Microfluidic approaches for making lipid NPs are mainly based on nanoprecipitation.…”

Section: Lipid Npsmentioning

confidence: 99%

“…It was demonstrated that the HFF method produced smaller lipid NPs with a more uniform structure. [96] HFF was also combined with passive mixing structures to achieve the self-assembly [91] Copyright 2021, The Royal Society of Chemistry. c) Schematic of an integrated baffle device composed of a lipid NP production region and a posttreatment region.…”

Section: Lipid Npsmentioning

confidence: 99%

See 3 more Smart Citations

Microfluidic Nanoparticles for Drug Delivery

Liu

Yang

Hui

et al. 2022

Small

View full text Add to dashboard Cite

Nanoparticles (NPs) have attracted tremendous interest in drug delivery in the past decades. Microfluidics offers a promising strategy for making NPs for drug delivery due to its capability in precisely controlling NP properties. The recent success of mRNA vaccines using microfluidics represents a big milestone for microfluidic NPs for pharmaceutical applications, and its rapid scaling up demonstrates the feasibility of using microfluidics for industrial‐scale manufacturing. This article provides a critical review of recent progress in microfluidic NPs for drug delivery. First, the synthesis of organic NPs using microfluidics focusing on typical microfluidic methods and their applications in making popular and clinically relevant NPs, such as liposomes, lipid NPs, and polymer NPs, as well as their synthesis mechanisms are summarized. Then, the microfluidic synthesis of several representative inorganic NPs (e.g., silica, metal, metal oxide, and quantum dots), and hybrid NPs is discussed. Lastly, the applications of microfluidic NPs for various drug delivery applications are presented.

show abstract

Section: Microfluidic Synthesis Of Organic Npsmentioning

confidence: 99%

“…[ 48 ] Similarly, comparing to the 2D‐iLiNP device, the 3D‐iLiNP device produced siRNA‐loaded lipid NPs with a more uniform size. [ 91 ]…”

Section: Microfluidic Synthesis Of Organic Npsmentioning

confidence: 99%

Section: Lipid Npsmentioning

confidence: 99%

Section: Lipid Npsmentioning

confidence: 99%

See 2 more Smart Citations

Microfluidic Nanoparticles for Drug Delivery

Liu

Yang

Hui

et al. 2022

Small

View full text Add to dashboard Cite

show abstract

“…Kenichi et al prepared core-shell nanoparticles through a novel way of two-step microfluidic-based mixing method [ 24 ]. In summary, microfluidic technology has broad prospects in lab-on-chip design and parameter adjustment as well as nanoformulation optimization [ 25 , 26 ]. However, in spite of research on polymer and lipid-based systems, to our knowledge, there is no report for a microfluidic-based cationic cholesterol derivatives/siRNA gene delivery nanosystem [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic-Based Cationic Cholesterol Lipid siRNA Delivery Nanosystem: Highly Efficient In Vitro Gene Silencing and the Intracellular Behavior

Zhu

Zhang

Sheng

et al. 2022

IJMS

View full text Add to dashboard Cite

Safe and efficient delivery of small interfering RNA (siRNA) is essential to gene therapy towards intervention of genetic diseases. Herein, we developed a novel cationic cholesterol lipid derivative (CEL) in which cholesterol hydrophobic skeleton was connected to L-lysine cationic headgroup via a hexanediol linker as the non-viral siRNA delivery carrier. Well-organized CEL/siRNA nanocomplexes (100–200 nm) were prepared by microfluidic-assisted assembly of CEL and siRNA at various N/P ratios. The CEL and CEL/siRNA nanocomplexes have lower cytotoxicity compared with bPEI25k. Delightfully, we disclosed that, in Hela–Luc and H1299–Luc cell lines, the micro-fluidic-based CEL/siRNA nanocomplexes exhibited high siRNA transfection efficiency under both serum-free condition (74–98%) and low-serum circumstances (80–87%), higher than that of lipofectamine 2000. These nanocomplexes also showed high cellular uptake through the caveolae/lipid-raft mediated endocytosis pathway, which may greatly contribute to transfection efficiency. Moreover, the time-dependent (0–12 h) dynamic intracellular imaging demonstrated the efficient delivery to cytoplasm after lysosomal co-localization. The results indicated that the microfluidic-based CEL/siRNA nanosystems possessed good stability, low cytotoxicity, high siRNA delivery efficiency, rapid cellular uptake and caveolae/lipid raft-dependent internalization. Additionally, this study provides a simple approach for preparing and applying a “helper lipid-free” cationic lipid siRNA delivery system as potential nanotherapeutics towards gene silencing treatment of (tumor) diseases.

show abstract

On the Influence of Fabrication Methods and Materials for mRNA‐LNP Production: From Size and Morphology to Internal Structure and mRNA Delivery Performance In Vitro and In Vivo

Bi,

Wilhelmy,

Unthan

et al. 2024

Adv Healthcare Materials

View full text Add to dashboard Cite

Lipid nanoparticle (LNP) remains the most advanced platform for messenger RNA (mRNA) delivery. To date, mRNA LNPs synthesis is mostly performed by mixing lipids and mRNA with microfluidics. In this study, a cost‐effective microfluidic setup for synthesizing mRNA LNPs is developed. It allows to fine‐tune the LNPs characteristics without compromising LNP properties. It is compared with a commercial device (NanoAssemblr) and ethanol injection and the influence of manufacturing conditions on the performance of mRNA LNPs is investigated. LNPs prepared by ethanol injection exhibit broader size distributions and more inhomogeneous internal structure (e.g., bleb‐like substructures), while other LNPs show uniform structure with dense cores. Small angel X‐ray scattering (SAXS) data indicate a tighter interaction between mRNA and lipids within LNPs synthesized by custom device, compared to LNPs produced by NanoAssemblr. Interestingly, the better transfection efficiency of polysarcosine (pSar)‐modified LNPs correlates with a higher surface roughness than that of PEGylated ones. The manufacturing approach, however, shows modest influence on mRNA expression in vivo. In summary, the home‐developed cost‐effective microfluidic device can synthesize LNPs and represents a potent alternative to NanoAssemblr. The preparation methods show notable effect on LNPs’ structure but a minor influence on mRNA delivery in vitro and in vivo.

show abstract

Three-dimensional, symmetrically assembled microfluidic device for lipid nanoparticle production

Abstract: We developed a three-dimensional and symmetrically assembled microfluidic device named the 3D-iLiNP device. The 3D-iLiNP device allowed the precise size control of sub-100 nm sized lipid nanoparticles by the homogeneous and slow ethanol dilution.

Cited by 24 publications

References 22 publications

Microfluidic Nanoparticles for Drug Delivery

Microfluidic Nanoparticles for Drug Delivery

Microfluidic-Based Cationic Cholesterol Lipid siRNA Delivery Nanosystem: Highly Efficient In Vitro Gene Silencing and the Intracellular Behavior

On the Influence of Fabrication Methods and Materials for mRNA‐LNP Production: From Size and Morphology to Internal Structure and mRNA Delivery Performance In Vitro and In Vivo

Contact Info

Product

Resources

About