Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform

Bailey‐Hytholt, Christina M.; Ghosh, Paroma; Dugas, Julia; Zarraga, Isidro E.; Bandekar, Amey

doi:10.3791/62226

Cited by 13 publications

(24 citation statements)

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“…In principal, assembly of LNPs is achieved by rapid mixing of four lipids in ethanol with RNA molecules in an aqueous buffer (near pH 4) in a microfluidic or T-junction mixer [ [47] , [48] , [49] ].…”

Section: Difference In Formulationmentioning

confidence: 99%

Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs

Suzuki

Ishiguro

2021

Drug Metabolism and Pharmacokinetics

163

101

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Nucleic acid therapeutics are developing into precise medicines that can manipulate specific genes. However, the development of safe and effective delivery system for the target cells has remained a challenge. Lipid nanoparticles (LNPs) have provided a revolutionary delivery system that can ensure multiple clinical translation of RNA-based candidates. In 2018, Patisiran (Onpattro) was first approved as an LNP-based siRNA drug. In 2020, during the coronavirus disease 2019 (COVID-19) outbreak, LNPs have enabled the development of two SARS-CoV-2 mRNA vaccines, Tozinameran (Comirnaty or Pfizer-BioNTech COVID-19 vaccine) and Elasomeran (Spikevax or COVID-19 vaccine Moderna) for conditional approval. Here, we reviewed the state-of-the-art LNP technology employed in three approved drugs (one siRNA-based and two mRNA-based drugs) and discussed the differences in their mode of action, formulation design, and biodistribution.

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Section: Difference In Formulationmentioning

confidence: 99%

Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs

Suzuki

Ishiguro

2021

Drug Metabolism and Pharmacokinetics

163

101

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“…Based on this principle, microfluidic mixing architectures have been developed with the aim of enhancing the mixing efficiency and attain a uniform population of LNPs while achieving excellent entrapment of the nucleic acid payload. [ 18c,82 ] Microfluidic mixing can be broadly categorized into passive and active mixing; passive mixers solely rely on the geometry of the microfluidic channels while active mixers control the flow of sample solutions by electrohydrodynamic disturbances. Within the context of LNP fabrication, most micromixers can be categorized as passive mixers.…”

Section: Lipid Nanoparticlesmentioning

confidence: 99%

Lipid Nanoparticle Technologies for Nucleic Acid Delivery: A Nanoarchitectonics Perspective

Ferhan

Park

et al. 2022

Adv Funct Materials

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Lipid-based nanoparticles have emerged as a clinically viable platform technology to deliver nucleic acids for a wide range of healthcare applications. Within this scope, one of the most exciting areas of recent progress and future innovation potential lies in the material science of lipid-based nanoparticles, both to refine existing nanoparticle strategies and to develop new ones. Herein, the latest efforts to develop next-generation lipid-based nanoparticles are covered by taking a nanoarchitectonics perspective and the design, nucleic acid encapsulation methods, scalable production, and application prospects are critically analyzed for three classes of lipid-based nanoparticles: 1) traditional lipid nanoparticles (LNPs); 2) lipoplexes; and 3) bicelles. Particular focus is placed on rationalizing how molecular self-assembly principles enable advanced functionalities along with comparing and contrasting the different nanoarchitectures. The current development status of each class of lipid-based nanoparticle is also evaluated and possible future directions in terms of overcoming clinical translation challenges and realizing new application opportunities are suggested.

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“…Lipid nanoparticles (LNPs) have attracted considerable research interest for encapsulating TNAs, especially due to their ionizable lipid presence, which is cationic at a low pH, thus, allowing complexation with negatively charged RNA or DNA [21,22]. Various generations of lipid nanocarriers have been tackled for TNAs delivery, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and cationic lipid-nucleic acid complexes [23].…”

Section: Lipid-based Delivery Systemsmentioning

confidence: 99%

“…For instance, Bailet-Hytholt et al [21] have synthesized LNPs encapsulated with mRNA or pDNA by means of a precise microfluidic mixing platform. Their experimental For instance, Gomez-Aguado et al [27] used the solvent emulsification-evaporation method to develop different solid lipid nanoparticles (SLNs) that combine cationic and ionizable lipids for the delivery of mRNA and pDNA.…”

Section: Lipid-based Delivery Systemsmentioning

confidence: 99%

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New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery

2021

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Nucleic acids represent a promising lead for engineering the immune system. However, naked DNA, mRNA, siRNA, and other nucleic acids are prone to enzymatic degradation and face challenges crossing the cell membrane. Therefore, increasing research has been recently focused on developing novel delivery systems that are able to overcome these drawbacks. Particular attention has been drawn to designing lipid and polymer-based nanoparticles that protect nucleic acids and ensure their targeted delivery, controlled release, and enhanced cellular uptake. In this respect, this review aims to present the recent advances in the field, highlighting the possibility of using these nanosystems for therapeutic and prophylactic purposes towards combatting a broad range of infectious, chronic, and genetic disorders.

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Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform

Cited by 13 publications

References 0 publications

Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs

Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs

Lipid Nanoparticle Technologies for Nucleic Acid Delivery: A Nanoarchitectonics Perspective

New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery

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