Lipid Nanoparticles for Drug and Gene Delivery: Advances, Limitations and Future Perspectives
DOI:
https://doi.org/10.22270/ajprd.v14i5.1870Abstract
Lipid nanoparticles (LNPs) have emerged as one of the most promising nanocarrier systems for the delivery of therapeutic agents, including conventional small-molecule drugs, proteins, messenger RNA (mRNA), small interfering RNA (siRNA), DNA, and gene-editing components. Their growing importance is attributed to their biocompatibility, versatility, ability to encapsulate and protect sensitive therapeutic molecules, and potential to facilitate intracellular delivery. LNPs generally consist of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG)-lipids, with each component contributing to particle formation, stability, biodistribution, cellular uptake, and therapeutic performance. The development of ionizable lipids has been particularly important because these lipids facilitate nucleic-acid encapsulation under acidic conditions while remaining relatively neutral at physiological pH, thereby reducing nonspecific interactions and toxicity. The clinical success of mRNA-LNP vaccines has provided strong evidence for the translational potential of this technology and has accelerated research into LNP-based therapeutics for cancer, infectious diseases, inherited disorders, and other conditions. Despite these advances, several challenges remain, including limited tissue-specific delivery, instability, immunogenicity, toxicity, endosomal entrapment, PEG-related limitations, manufacturing complexity, and regulatory requirements. This review discusses the principles, composition, preparation methods, mechanisms, therapeutic applications, recent advances, limitations, and future perspectives of lipid nanoparticles for drug and gene delivery, with particular emphasis on nucleic-acid therapeutics, targeted delivery, organ-selective LNPs, and emerging technologies.
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