Rapid-mixing production of lipid nanoparticles for biomolecules delivery

Abstract

Abstract During past years, lipid nanoparticles (LNPs) have emerged as helpful tool to deliver sensible biomolecules such as protein and oligonucleotides demonstrating high efficiency in vitro and in vivo. However, the translation of these nanosystems from bench to bedside has been limited mainly because the LNPs production methods are usually associated to poor control over the lipid’s assembly and hence LNPs quality attributes. In this framework, microfluidics offers the opportunity to overcome this issue since it allows fast, reproducible, and robust LNPs production and now it is revolutionizing the R&D sections since it is the ideal choice for a rapid prototyping of a formulation. New microfluidic platforms need to be developed and customized considering the production process. Within the present work, the feasibility of producing LNPs by a brand-new microfluidic platform was demonstrated by a systematic approach. Screening design of experiment and Box-Behnken design were applied to identify the operating parameters affecting the LNPs quality. The performances of the new production platform were assessed by producing neutral, stealth, and cationic LNPs and further, several model biomolecules were successfully loaded with a high encapsulation always higher than 70%.