Lab-scale production of an MRNA lipid nanoparticle delivery platform for targeting Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) has the worst 5-year survival rate of any human cancer type. What makes this highly aggressive type of pancreatic cancer unique is its highly fibrotic environment around the tumor cells. Cancer-associated fibroblasts (CAFs) deposit excessive extracellular matrix (ECM), preventing treatments reaching their target. Lack of successful therapies required a fresh approach. COVID-19 messenger ribonucleic acid (mRNA) technology caused a massive uprise in potential when used in lipid nanoparticles (LNPs). Solely delivering mRNA is not effective, as it is vulnerable to ribonucleases and are unable to effectively penetrate the cell membrane. This study provides a deep background study on LNPs and aims at optimizing a lipid nanoparticle (LNP) platform for targeting PDAC. Total flow rate (TFR) and microfluidic mixing methods were used as parameters to optimize LNP size and encapsulation efficiency. Conjugating a targeting ligand to a therapeutic has the potential of increasing accumulation at the targeted site from 0.1% to 5%. That is why two conjugation techniques were used for creating targeted LNPs. The in vitro uptake and transfection studies showed cellular uptake and green fluorescent protein (GFP) expression.