Microfluidics: a transformational tool for nanomedicine development and production

Abstract

Microfluidic devices are mircoscale fluidic circuits used to manipulate liquids at the nanoliter scale. The ability to control the mixing of fluids and the continuous nature of the process make it apt for solvent/antisolvent precipitation of drug-delivery nanoparticles. This review describes the use of numerous microfluidic designs for the formulation and production of lipid nanoparticles, liposomes and polymer nanoparticles to encapsulate and deliver small molecule or genetic payloads. The advantages of microfluidics are illustrated through examples from literature comparing conventional processes such as beaker and T-tube mixing to microfluidic approaches. Particular emphasis is placed on examples of microfluidic nanoparticle formulations that have been tested in vitro and in vivo. Fine control of process parameters afforded by microfluidics, allows unprecedented optimization of nanoparticle quality and encapsulation efficiency. Automation improves the reproducibility and optimization of formulations. Furthermore, the continuous nature of the microfluidic process is inherently scalable, allowing optimization at low volumes, which is advantageous with scarce or costly materials, as well as scale-up through process parallelization. Given these advantages, microfluidics is poised to become the new paradigm for nanomedicine formulation and production.

Keywords:

• Liposomes
• microfluidic mixing
• nanoparticles
• RNAi
• siRNA

Acknowledgements

The authors would like to thank Dr. Grace Tharmarajah for her valuable input in the preparation of this manuscript.

The authors would further like to express their gratitude to Dr. Pieter Cullis for providing valuable background contributions to this new nanoparticle technology, through his lifelong commitment in the field of lipid-based nanoparticle drug development.

Disclosure statement

The authors of this manuscript are employees of the Precision NanoSystems, Inc., who owns the NanoAssemblr^TM Platform for the microfluidic manufacture of nanoparticles. Dr Euan Ramsay is a stakeholder of the company.