Paroor Sandra, Shaji Ashwin T, Bino Leah, Praveen Navya G, Unnipurath Swathi, Anil Parvathy, Geo Rosmy, Nagamalleswari Easa, Bonam Srinivasa Reddy, Kurapati Rajendra
School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram, Maruthamala PO, Vithura, Kerala, India.
MTCC and Gene Bank, CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh, India.
Methods Mol Biol. 2025;2965:341-354. doi: 10.1007/978-1-0716-4742-4_16.
The development of lipid-based nanoparticles (LNPs) has significantly advanced the field of drug delivery, particularly for nucleic acids, such as mRNA being clinically used in the vaccines against COVID-19. This chapter explores the structural composition and functional properties of LNPs, including key components, such as ionizable cationic lipids, neutral/helper phospholipids, cholesterol, and lipid-anchored polyethylene glycol (PEG) constructs. The discussion includes the role of these components in improving the stability, biocompatibility, and delivery efficiency of LNPs. Special attention is given to the role of ionizable lipids in mRNA delivery, including their pH sensitivity, structural variations, and the implications for endosomal escape and cytosolic release. The chapter also examines the progression from classical lipid carriers to specialized LNP designs, emphasizing the importance of self-assembly properties, preparation methods, and recent advancements in LNP production techniques, including microfluidics, impinging-jet mixing, ethanol dilution, manual mixing, and T-junction blending. The clinical applications of LNPs, particularly in mRNA vaccine development, cancer vaccines, and infectious disease vaccines, are also touched upon.
基于脂质的纳米颗粒(LNPs)的发展极大地推动了药物递送领域,特别是对于核酸而言,例如在针对COVID-19的疫苗中临床使用的mRNA。本章探讨了LNPs的结构组成和功能特性,包括关键成分,如可电离阳离子脂质、中性/辅助磷脂、胆固醇和脂质锚定聚乙二醇(PEG)构建体。讨论内容包括这些成分在提高LNPs的稳定性、生物相容性和递送效率方面的作用。特别关注可电离脂质在mRNA递送中的作用,包括它们的pH敏感性、结构变化以及对内体逃逸和胞质释放的影响。本章还研究了从经典脂质载体到特殊LNP设计的进展,强调了自组装特性、制备方法以及LNP生产技术的最新进展的重要性,包括微流体技术、冲击射流混合、乙醇稀释、手动混合和T型接头混合。LNPs的临床应用,特别是在mRNA疫苗开发、癌症疫苗和传染病疫苗中的应用也有所涉及。
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