Drug & Compound Encapsulation Pack

Application notes

• How to prepare PLGA nanoparticle by hydrodynamic flow focusing
• Nanoparticle generator
• Synthetic Organelles
• Nanoparticles & nanohydrogels
• Encapsulation
• Drug-delivery
• How does microfluidics alginate beads production work?

All our application notes

Reviews

• Liposome and Lipid nanoparticle | An overview
• Microfluidics for PLGA nanoparticle synthesis: A review
• Introduction to droplet-based microfluidics
• Droplets encapsulation for biological applications: a review
• Droplet production methods
• Sodium Alginate and applications: a review

All our reviews 

Microfluidics herringbone lipid nanoprecipitation principle

Ribonucleic acid (RNA) is a critical polymeric molecule for the regulation and expression of genes. RNA interference (RNAi) is a method that silences genes by using sequence-specific small interfering RNA (siRNA). Based on their mRNA counterpart nucleotide sequences siRNAs block the production of specific proteins [1-3]. To deliver siRNA for therapeutic applications, lipid nanoparticles (LNP) are the most commonly used system for in vivo applications like anti-tumor agent or polyneuropathies treatment [4-5].
The BioNTech/Pfizer’s BNT162b2 and Moderna’s mRNA-1273 vaccines also use lipid nanoparticles as vehicles for mRNA delivery into the cytoplasm of host cells that lead to the production of COVID-neutralizing antibodies [5]. Thus, lipid nanoparticle synthesis have played a critical role in the development of COVID-19 vaccines and other nanomedicines and are considered to be very promising for the development of new drug delivery systems [6].

Lipid nanoparticles can be used for other applications like using solid lipid nanoparticle (SLN) as cosmetic delivery systems [7].

The lipid nanoparticle synthesis pack includes staggered herringbone micromixers that create chaotic flows. They are the most commonly used microfluidic chips for LNP synthesis [8]. The structure generates chaotic advection which is able to induce rapid mixing at Reynolds numbers smaller than 1 [9] thus allowing a better encapsulation efficiency than bulk methods [10].

Lipid nanoparticle (LNP) formulation example

1. Whitehead, K., Langer, R. & Anderson, D. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8, 129–138 (2009).
2. Belliveau N., Huft J., Lin P., Chen S., Leung A., Leaver T., Wild A., Lee J., Taylor R., Tam Y., Hansen C., Cullis P., Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for In Vivo Delivery of siRNA, Molecular Therapy – Nucleic Acids, 1, 2012, e37, 2162-2531
3. Allen, Theresa M., and Pieter R. Cullis. “Drug delivery systems: entering the mainstream.” Science 303.5665 (2004), 1818-1822.
4. Sasayama Y., Hasegawa M., Taguchi E., Kubota K., Kuboyama T., Naoi T., Yabuuchi H., Shimai N., Asano M., Tokunaga A., Ishii T., Enokizono J., 2019, In vivo activation of PEGylated long circulating lipid nanoparticle to achieve efficient siRNA delivery and target gene knock down in solid tumors. Journal of Controlled Release
5. Let’s talk about lipid nanoparticles. Nat Rev Mater 6, 99 (2021).
6. Thi, T.T.H.; Suys, E.J.A.; Lee, J.S.; Nguyen, D.H.; Park, K.D.; Truong, N.P. Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines. Vaccines 2021, 9, 359
7. Sylvia A Wissing; Rainer H Müller (2003). Cosmetic applications for solid lipid nanoparticles (SLN), 254(1), 65–68.
8. Maeki M., Kimura N., Sato Y., Harashima H., Tokeshi M., 2018, Advances in microfluidics for lipid nanoparticles and extracellular vesicles and applications in drug delivery systems. Advanced Drug Delivery Reviews
9. N-T. Nguyen, Z. Wu, Micromixers-a review, J. Micromech. Microeng. 15, 2005, R1-R16.
10. Leung A., Hafez I., Baoukina S., Belliveau S., Zhigaltsev I., Afshinmanesh E., Tieleman P., Hansen C., Hope M., and Cullis P., The Journal of Physical Chemistry C 2012 116 (34), 18440-18450

The amazing benefits of microfluidics can be applied to many Liposome and Lipid Nanoparticle applications and therefore the content of the Liposome and Lipid Nanoparticle Synthesis Pack can be adjusted to suit your specific needs!

Full control over key parameters impacting the mixing

There are a few ways to generate lipid nanoparticles in microfluidics. In any case, the most important part relies on the fast mixing of two phases (organic and aqueous). The more efficient and homogeneous the mixing is, the better the control over the size and its distribution. The following figure illustrates how the speed of mixing influences the LNPs size; a slow dilution of the ethanol phase (a) leads to large particles in comparison with a faster dilution (b).

Micromixing chips

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