Using Microfluidics for Scalable Manufacturing of Nanomedicines from Bench to GMP: A Case Study Using Protein-loaded Liposomes


Authors: C. Webb, N. Forbes, C.B. Roces, G. Anderluzzi, G. Lou, S. Abraham, L. Ingalls, K. Marshall, T.J. Leaver, J.A. Watts, J.W. Aylott, and Y. Perrie

Journal: International Journal of Pharmaceutics

DOI: 10.1016/j.ijpharm.2020.119266

Publication - Abstract

April 03, 2020

Abstract

In a 2020 study conducted by researchers at the University of Strathclyde Institute of Pharmacy and Biomedical Sciences, a scale-by-scale development of genetic medicines from bench to GMP was outlined through the generation of liposomes with a protein payload using two different laminar flow based microfluidic mixers operating on the NanoAssemblr® Benchtop, IgniteTM, or NxGen BlazeTM and GMP platforms. Despite differences in mixer design, given that the NanoAssemblr® Benchtop operates a herringbone mixer, and the IgniteTM, NxGen BlazeTM/GMP utilizes a toroidal mixer, both systems were shown to produce liposomes with consistent physiochemical characteristics across a range of formulations. Webb et al. showcased the functionality of the toroidal mixer and its advantages that can lead to higher product volumes meeting GMP standards, higher throughput, and a lower cost of production without compromising quality, fine-tunable synthesis, size control, or batch-to-batch homogeneity seen in particles generated from the herringbone mixer of the NanoAssemblr® Benchtop. 

Characteristics like particle size, polydispersity index (PDI) and zeta potential were compared for liposomes generated by each mixer to better assess for changes in factors that are integral for the development of safe drug candidates, such as, liposome internal lipid concentration, protein entrapment efficiency, nucleic acid efficiency, drug encapsulation efficiency and payload release. The paper demonstrates no significant differences in key liposome characteristics between the two mixers and highlights the enhanced scalability of the NxGen toroidal mixer as attributed by its design encompassing circular structures that lead to an increased number of vortices. This design eliminates the need for parallelization of multiple mixers, and production of micro-scale structures within the herringbone mixer to facilitate mixing, therefore, resulting in faster production of volumes that meet GMP standards. This research not only exemplifies quicker production speeds and volumes of the toroidal mixer within the NxGen platforms: IgniteTM, BlazeTM, GMP but also demonstrates great reproducibility in liposome particle generation fundamental to greater advancements in future studies that aim to progress novel drug candidates from bench into an impactful commercial product at the GMP stage.

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