A strategy for synthesis of lipid nanoparticles using microfluidic devices with a mixer structure

Maeki, Masatoshi; Saito, Tomohisa; Sato, Yusuke; Yasui, Takahiro; Kaji, Noritada; Ishida, Akihiko; Tani, Hirofumi; Baba, Yoshinobu; Harashima, Hideyoshi; Tokeshi, Manabu

doi:10.1039/c5ra04690d

Cited by 90 publications

(70 citation statements)

References 35 publications

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“…The generation of self-assembled nanoparticles using this device is promising. Examples include lipid nanoparticles, 20) polymer nanoparticles, [21][22][23] non-ionic surfactant nanoparticles 24) and cochleate microparticles. 25) To date, most applications have focused on the preparation of liposomes [26][27][28] and there is little information regarding the generation of other types of nanoparticles using this approach.…”

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confidence: 99%

The Use of an Efficient Microfluidic Mixing System for Generating Stabilized Polymeric Nanoparticles for Controlled Drug Release

Morikawa

Tagami

Hoshikawa

et al. 2018

Biological & Pharmaceutical Bulletin

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Microfluidics is a promising system for efficiently optimizing the experimental conditions for preparing nanomedicines, such as self-assembled nanoparticles. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are promising drug carriers allowing sustained drug release. Here, we encapsulated the model drug curcumin, which has many pharmacological activities, into PLGA nanoparticles and investigated the effects of experimental conditions on the resulting PLGA nanoparticles using a microfluidics system with a staggered herringbone structure that can stir solutions through chaotic advection. The total flow rate and flow rate ratio of the solutions in the microfluidics system affected the diameters, polydispersity index, and encapsulation efficiency of the resulting PLGA nanoparticles and produced small, homogenous PLGA nanoparticles. The incorporation of polyethylene glycol (PEG)-PLGA into the PLGA nanoparticles reduced the particle size and improved the encapsulation efficiency. Initial burst release from the PLGA nanoparticles was prevented by the incorporation of PEG2000-PLGA. Curcumin-loaded PEGylated PLGA nanoparticles showed cytotoxicity similar to that of other formulations. This microfluidics system allows high throughput and is scalable for the efficient preparation of PLGA nanoparticles and PEGylated PLGA nanoparticles. Our results will be useful for developing novel PLGA-based polymer nanoparticles by using the microfluidics.

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confidence: 99%

The Use of an Efficient Microfluidic Mixing System for Generating Stabilized Polymeric Nanoparticles for Controlled Drug Release

Morikawa

Tagami

Hoshikawa

et al. 2018

Biological & Pharmaceutical Bulletin

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Section: Microfluidics For Fabrication Of Sddss With Well‐controlledmentioning

confidence: 99%

“…Other mixing strategies in microfluidic devices have also been applied to fabricate self‐assemblies. To enhance mixing efficiency, microchannels have been engineered with special architectures, such as Tesla (Figure D) and herringbone (Figure E) structures. The flow of fluid through these microstructures induces turbulence, increasing the volume of solutes transported over the cross section of the microchannel .…”

Section: Microfluidics For Fabrication Of Sddss With Well‐controlledmentioning

confidence: 99%

“…Besides diffusive mixing, other microfluidic mixing strategies have also been reported for controlling sDDS size and dispersity. Maeki demonstrated that rapid mixing in a staggered herringbone micromixer (SHM) results in improved lipid‐NP formation (Figure E). The size of liposomes can be precisely controlled (35–150 nm), by varying the SHM cycle numbers and the flow‐rate ratio of the aqueous solution and the lipid/ethanol solution.…”

Section: Microfluidics For Fabrication Of Sddss With Well‐controlledmentioning

confidence: 99%

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Microfluidics for Cancer Nanomedicine: From Fabrication to Evaluation

Zhang

Zhu

Shen

2018

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Self-assembled drug delivery systems (sDDSs), made from nanocarriers and drugs, are one of the major types of nanomedicines, many of which are in clinical use, under preclinical investigation, or in clinical trials. One of the hurdles of this type of nanomedicine in real applications is the inherent complexity of their fabrication processes, which generally lack precise control over the sDDS structures and the batch-to-batch reproducibility. Furthermore, the classic 2D in vitro cell model, monolayer cell culture, has been used to evaluate sDDSs. However, 2D cell culture cannot adequately replicate in vivo tissue-level structures and their highly complex dynamic 3D environments, nor can it simulate their functions. Thus, evaluations using 2D cell culture often cannot correctly correlate with sDDS behaviors and effects in humans. Microfluidic technology offers novel solutions to overcome these problems and facilitates studying the structure-performance relationships for sDDS developments. In this Review, recent advances in microfluidics for 1) fabrication of sDDSs with well-defined physicochemical properties, such as size, shape, rigidity, and drug-loading efficiency, and 2) fabrication of 3D-cell cultures as "tissue/organ-on-a-chip" platforms for evaluations of sDDS biological performance are in focus.

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“…The microdevice was fabricated by standard softlithography techniques with PDMS and a glass slide. 16 The microdevice had microchannels with individual inlets and outlets to hold four different samples. Each microchannel is 300 µm wide and 1 mm deep with <1 µl sample volume.…”

Section: The Instrumentmentioning

confidence: 99%

A compact fluorescence polarization analyzer with high-transmittance liquid crystal layer

Wakao

Satou²,

Nakamura

et al. 2018

Review of Scientific Instruments

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Fluorescence polarization (FP) offers easy operation and rapid processing, making it implementable in molecular interaction analysis. Previously we have developed a unique FP measurement system using a liquid crystal (LC) layer and an image sensor. The system is based on a principle of synchronized detection between the switching rate of the LC layer and the sampling rate of the CCD. The FP system realized simultaneous multiple sample detection; however, the measurement precision was lower than that of the conventional FP apparatus. The main drawbacks were low light transmittance of the LC layer and insufficient synchronization between the LC layer and CCD. In this paper, we developed a new FP analyzer based on LC-CCD synchronization detection. By using a newly designed LC with high transmittance and improving synchronization, the performance of the system has been dramatically improved. Additionally, we reduced the cost by using an inexpensive CCD and an LED as the excitation source. Simultaneous FP immunoassay of multiple samples of prostaglandin E2 was performed. The error rate of the FP system is reduced from 16.9% to 3.9%, as comparable to the commercial conventional FP system.

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A strategy for synthesis of lipid nanoparticles using microfluidic devices with a mixer structure

Cited by 90 publications

References 35 publications

The Use of an Efficient Microfluidic Mixing System for Generating Stabilized Polymeric Nanoparticles for Controlled Drug Release

The Use of an Efficient Microfluidic Mixing System for Generating Stabilized Polymeric Nanoparticles for Controlled Drug Release

Microfluidics for Cancer Nanomedicine: From Fabrication to Evaluation

A compact fluorescence polarization analyzer with high-transmittance liquid crystal layer

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