(161) A dive into optimization of novel ionizable lipid nanoparticles for enhanced siRNA delivery
Introduction: FDA-approved siRNA and COVID-19 mRNA therapeutics highlight lipid nanoparticles (LNP) as promising delivery modalities. Optimizing LNP composition & processing is key to maximizing efficacy. LNPs encapsulate siRNA via electrostatic interactions between ionizable cationic lipids & anionic siRNA. However, their commercial use is limited to liver delivery, with challenges in tumor targeting & cargo release. We developed a novel ionizable cationic lipid (NLD) LNP to enhance siRNA internalization & endosomal release for improved cancer therapy, comparing it to the gold standard, Dlin-DMA-MC3 (MC3).
Learning Objectives:
Understand the process parameters driving the LNP physicochemical properties and its efficacy
Evaluate the interplay of LNP composition and loading capacity to maximize the efficacy and safety
Identify the challenges with siRNA-LNP tumor delivery & facilitating cargo endosomal release
