LIPID NANOPARTICLE (LNPs) FOR mRNA DELIVERY: PRINCIPLES, ADVANCES, AND APPLICATIONS

Lipid nanoparticles (LNPs) have emerged as the leading platform for the safe and efficient delivery of messenger RNA (mRNA) therapeutics. This book chapter explores the structural composition, mechanisms of delivery, and recent advancements in LNP-based mRNA systems. LNPs typically comprise four key lipid components: ionizable cationic lipids, phospholipids, cholesterol, and PEGylated lipids. Each of these components contributes to mRNA encapsulation, protection, stability, and intracellular delivery. Ionizable lipids facilitate endosomal escape and cytoplasmic release of mRNA, while phospholipids and cholesterol enhance membrane integrity and stability. PEGylated lipids extend circulation time and prevent aggregation. The mechanisms of LNP-mediated mRNA delivery involve protection against ribonuclease degradation, endocytosis-mediated cellular uptake, endosomal escape, and cytoplasmic translation of mRNA into therapeutic proteins. Technological advances, including biodegradable lipids, self-amplifying RNA (saRNA), and microfluidic manufacturing, have improved biocompatibility, dosage efficiency, and reproducibility. These developments have expanded LNP applications beyond COVID-19 vaccines to gene editing, protein replacement, and cancer immunotherapy, offering tunable platforms for precise and safe mRNA delivery across biomedical disciplines.