Microfluidic Synthesis of Scalable Layer-by-Layer Multiple Antigen Nano-Delivery Platform for SARS-CoV-2 Vaccines

Abstract

The COVID-19 outbreak was a global pandemic with wide-ranging healthcare implications. Although several mRNA-based vaccines delivered using lipid nanoparticles (LNP) have been approved and demonstrated efficacy at reducing the severity and spread of infection, continued rapid viral evolution and disadvantages currently associated with LNP delivery vehicles (such as toxicity) are driving the design of next-generation SARS-CoV-2 vaccines. Herein, we describe the development of a trimethylated chitosan-based nanoparticle layer-by-layer (LbL) delivery platform for multiple antigens as a scalable and safe COVID-19 vaccine, known as, “LbL-CoV19”. These vaccine candidates have been demonstrated to be biocompatible, safe, and effective at stimulating both humoral and cellular responses for protection in preclinical studies. Preliminary results also indicate that LbL-CoV19 can potentially achieve rapid, long-lasting, and broad protection against the SARS-CoV-2 challenge. The “plug-and-play” platform technology is well suited to preparedness for future pandemics and disease outbreaks.

Modulating the Nature of Ionizable Lipids and Number of Layers in Hyaluronan-Decorated Lipid Nanoparticles for In Vitro Delivery of RNAi

“…These advantages can be expanded to other polyanions, as the outermost layer plays an important role in the intracellular trafficking of nanoparticles and their in vivo biodistribution [ 41 , 42 ]. Finally, ongoing research has been demonstrating the feasibility of developing LbL or their closely related core–shell-assemble nanoparticles by microfluidics [ 43 , 44 ], which is a technique that could be scaled up for industrial applications. Therefore, this investigation sheds light on the applicability of the LbL strategy to modulate the properties of LNPs, the gold standard gene delivery platform to date.…”