Microfabrication and microfluidic devices for drug delivery

Kimura, Niko; Maeki, Masatoshi

doi:10.1016/b978-0-12-812659-2.00005-3

Cited by 7 publications

(9 citation statements)

References 61 publications

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“…The first approved siRNA medicine-encapsulated LNPs have been marketed as Onpattro, which is produced using the microfluidic-based ethanol injection method. Microfluidic devices with herringbone micromixer structures have been widely used for the preparation of size-controlled LNPs. − Recently, we have developed a microfluidic device equipped with baffle structures for the production of precise size-tuned LNPs . The microfluidic device with baffle structures showed many advantages for LNP production, including its simple structure, a wide range of LNP size controllability from 20 to 100 nm, and realization of an integrated LNP production process.…”

Section: Introductionmentioning

confidence: 99%

Development of a Microfluidic-Based Post-Treatment Process for Size-Controlled Lipid Nanoparticles and Application to siRNA Delivery

Kimura

Maeki

Sato

et al. 2020

ACS Appl. Mater. Interfaces

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Microfluidic methodologies for preparation of lipid nanoparticles (LNPs) based on an organic solvent injection method enable precise size control of the LNPs. After preparation of LNPs, the organic solvent injection method needs some post-treatments, such as overnight dialysis or direct dilution with a buffer solution. LNP production using the microfluidic-based organic solvent injection method is dominated by kinetics rather than thermodynamics. Kinetics of ethanol removal from the inner and outer membranes of LNPs could induce a structural change in the membrane that could lead to fusion of LNPs. However, the effects of microfluidic post-treatment on the final size of LNPs have not been sufficiently understood. Herein, we investigated the effect of the post-treatment processes on the final product size of LNPs in detail. A simple baffle device and a model lipid system composed of a neutral phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC) and cholesterol were used to produce the LNPs. We demonstrated that flow conditions of the post-treatment diluting the remaining ethanol in the LNP suspension affected the final product size of LNPs. Based on the findings, we developed an integrated baffle device composed of an LNP production region and a post-treatment region for a microfluidic-based LNP production system; this integrated baffle device prevented the undesirable aggregation or fusion of POPC LNPs even for the high-lipid-concentration condition. Finally, we applied our concept to small interfering RNA (siRNA) delivery and confirmed that no significant effects due to the continuous process occurred on the siRNA encapsulation efficiency, biological distribution, and knockdown activity. The microfluidic post-treatment method is expected to contribute to the production of LNPs for practical applications and the development of novel LNP-based nanomedicines.

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Section: Introductionmentioning

confidence: 99%

Development of a Microfluidic-Based Post-Treatment Process for Size-Controlled Lipid Nanoparticles and Application to siRNA Delivery

Kimura

Maeki

Sato

et al. 2020

ACS Appl. Mater. Interfaces

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“…Other membrane types with specific attributes can also be developed for this application. 26,[45][46][47][48][49] Diffusion-controlled drug delivery can be achieved from a CED device by switching the operation mode. 50 This is however difficult to achieve without fine pressure control.…”

Section: Drug Delivery Approachesmentioning

confidence: 99%

Fluidic enabled bioelectronic implants: opportunities and challenges

et al. 2022

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“…29 Lastly, being a continuous process, microfluidic protocols are easy to scale to large-scale production by using parallel chips to allow for mass production. 31 Pumping liquids into a total of only six chips resulted in nanoparticle dispersion with a production rate of 72 mL/min; using more chips is expected to further expedite the nanoparticle production process for higher throughput on the industrial scale. 27 In addition, novel chips such as toroidal mixer can allow high throughput production of up to 200 mL/ min.…”

Section: T H Imentioning

confidence: 99%

“…High throughput screening a library of lipids for efficient assembly of nucleic acid loaded LNPs is enabled using microfluidic platforms by utilizing lipids minimally. 31 There has been a general consensus among drug delivery researchers, especially after the FDA approval of Onpattro and COVID-19 vaccines, that there are four main lipid components in a successful LNPs aside from nucleic acids: ionizable lipid, PEGylated lipid, neutral lipid, and cholesterol. The exact composition of the FDA-approved nucleic acid-loaded LNPs is provided in Table 3.…”

Section: Microfluidic Staggered Herringbone Micromixers (Shms)mentioning

confidence: 99%

Microfluidics for Development of Lipid Nanoparticles: Paving the Way for Nucleic Acids to the Clinic

Ali

Hooshmand

El‐Sayed

2021

ACS Appl. Bio Mater.

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Nucleic acid therapeutics hold an unprecedented promise toward treating many challenging diseases; however, their use is hampered by delivery issues. Microfluidics, dealing with fluids in the microscale dimensions, have provided a robust means to screening raw materials for development of nano delivery vectors, in addition to controlling their size and minimizing their polydispersity. In this mini-review, we are briefly highlighting the different types of nucleic acid therapies with emphasis on the delivery requirement for each type. We provide a thorough review of available methods for the development of nanoparticles, especially lipid nanoparticles (LNPs) that resulted in FDA approval of the first ever nucleic acid nanomedicine. We then focus on recent research attempts for how microfluidic synthesis of lipid nanoparticles and discuss the various parameters required for successful formulation of LPNs including chip design, flow regimes, and lipid composition. We then identify key areas of research in microfluidics and related fields that require attention for future success in clinical translation of nucleic acid nanomedicines.

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Microfabrication and microfluidic devices for drug delivery

Cited by 7 publications

References 61 publications

Development of a Microfluidic-Based Post-Treatment Process for Size-Controlled Lipid Nanoparticles and Application to siRNA Delivery

Development of a Microfluidic-Based Post-Treatment Process for Size-Controlled Lipid Nanoparticles and Application to siRNA Delivery

Fluidic enabled bioelectronic implants: opportunities and challenges

Microfluidics for Development of Lipid Nanoparticles: Paving the Way for Nucleic Acids to the Clinic

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