Microfluidic technologies and devices for lipid nanoparticle-based RNA delivery

Maeki, Masatoshi; Uno, Shuya; Niwa, Ayuka; Okada, Yuto; Tokeshi, Manabu

doi:10.1016/j.jconrel.2022.02.017

Cited by 162 publications

(96 citation statements)

References 110 publications

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“…The size-dependent cellular uptake in different cell lines has been widely demonstrated, − and this has greatly encouraged the advancement of size-targeted therapeutic regimens via precise particle size modulation. Microfluidic devices can precisely modulate minimal fluid volumes in microscale-controlled channels to prepare particles with controlled sizes and great batch-to-batch reproducibility. − Furthermore, microfluidic-based nanoprecipitation allows for the use of expensive therapeutics in small volumes to screen different experimental conditions and to develop optimal formulations of NP-based nanomedicines. For the preparation of NPs using the nanoprecipitation method, the solvent effect is a significant factor in controlling the NP size and encapsulating hydrophobic drugs .…”

Section: Introductionmentioning

confidence: 99%

Effect of Organic Solvents on a Production of PLGA-Based Drug-Loaded Nanoparticles Using a Microfluidic Device

et al. 2022

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The translation of nanoparticles (NPs) from laboratory to clinical settings is limited, which is not ideal. One of the reasons for this is that we currently have limited ability to precisely regulate various physicochemical parameters of nanoparticles. This has made it difficult to rapidly perform targeted screening of drug preparation conditions. In this study, we attempted to broaden the range of preparation conditions for particle size-modulated poly(lactic- co -glycolic-acid) (PLGA) NP to enhance their applicability for drug delivery systems (DDS). This was done using a variety of organic solvents and a glass-based microfluidic device. Furthermore, we compared the PDMS-based microfluidic device to the glass-based microfluidic device in terms of the possibility of a wider range of preparation conditions, especially the effect of different solvents on the size of the PLGA NPs. PLGA NPs with different sizes (sub-200 nm) were successfully prepared, and three different types of taxanes were employed for encapsulation. The drug-loaded NPs showed size-dependent cytotoxicity in cellular assays, regardless of the taxane drug used.

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Section: Introductionmentioning

confidence: 99%

Effect of Organic Solvents on a Production of PLGA-Based Drug-Loaded Nanoparticles Using a Microfluidic Device

et al. 2022

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“…Meanwhile, recent breakthroughs in LNPs have come from the incorporation of ionizable lipid technologies and microfluidic devices (Fig. 4 B) [ 88 ].…”

Section: Prevention For Covid-19mentioning

confidence: 99%

A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies

Kumari

et al. 2022

J Biomed Sci

101

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The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.

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“…Figs 2 and S1 show the NP sizes and size distributions. In the case of lipid nanoparticles (LNPs), small-sized LNPs formed under high TFR and FRR conditions [24][25][26][27]. The PLGA NP size also decreased with an increase in the TFR, maintaining a single peak.…”

Section: Effect Of the Flow Conditions On Np Sizementioning

confidence: 99%

Preparation of size-tunable sub-200 nm PLGA-based nanoparticles with a wide size range using a microfluidic platform

Bao

Maeki²,

Ishida³

et al. 2022

PLoS ONE

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The realization of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) from laboratory to clinical applications remains slow, partly because of the lack of precise control of each condition in the preparation process and the rich selectivity of nanoparticles with diverse characteristics. Employing PLGA NPs to establish a large range of size-controlled drug delivery systems and achieve size-selective drug delivery targeting remains a challenge for therapeutic development for different diseases. In this study, we employed a microfluidic device to control the size of PLGA NPs. PLGA, poly (ethylene glycol)-methyl ether block poly (lactic-co-glycolide) (PEG-PLGA), and blend (PLGA + PEG-PLGA) NPs were engineered with defined sizes. Blend NPs exhibit the widest size range (40–114 nm) by simply changing the flow rate conditions without changing the precursor (polymer molecular weight, concentration, and chain segment composition). A model hydrophobic drug, paclitaxel (PTX), was encapsulated in the NPs, and the PTX-loaded NPs maintained a large range of controllable NP sizes. Furthermore, size-controlled NPs were used to investigate the effect of particle size of sub-200 nm NPs on tumor cell growth. The 52 nm NPs showed higher cell growth inhibition than 109 nm NPs. Our method allows the preparation of biodegradable NPs with a large size range without changing polymer precursors as well as the nondemanding fluid conditions. In addition, our model can be applied to elucidate the role of particle sizes of sub-200 nm particles in various biomedical applications, which may help develop suitable drugs for different diseases.

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Microfluidic technologies and devices for lipid nanoparticle-based RNA delivery

Cited by 162 publications

References 110 publications

Effect of Organic Solvents on a Production of PLGA-Based Drug-Loaded Nanoparticles Using a Microfluidic Device

Effect of Organic Solvents on a Production of PLGA-Based Drug-Loaded Nanoparticles Using a Microfluidic Device

A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies

Preparation of size-tunable sub-200 nm PLGA-based nanoparticles with a wide size range using a microfluidic platform

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