A tale of nucleic acid-ionizable lipid nanoparticles: Design and manufacturing technology and advancement.

IF 5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Anindita De, Young Tag Ko
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引用次数: 3

Abstract

ABSTRACT Introduction Ionizable lipid nanoparticles (LNPs) have been proven to have high encapsulation, cellular uptake, and effective endosomal escape and are therefore promising for nucleic acid delivery. The combination of ionizable lipids, helper lipids, cholesterol, and PEG lipids advances nucleic acid-ionizable LNPs and distinguishes them from liposomes, SLNs, NLCs, and other lipid particles. Solvent injection and microfluidics technology are the primary manufacturing techniques for commercialized ionizable LNPs. Microfluidics technology limitations restrict the rapid industrial scale-up and therapeutic effectiveness of ionized LNPs. Alternative manufacturing technologies and target-specific lipids are urgently needed. Area covered This article provides an in-depth update on the lipid compositions, clinical trials, and manufacturing technologies for nucleic acid-ionizable LNPs. For the first time, we updated the distinction between ionizable LNPs and other lipid particles. We also proposed an alternate thermocycling technology for high industrial scale-up and the stability of nucleic acid-ionizing LNPs. Expert opinion Nucleic acid-ionizable LNPs have a promising future for delivering nucleic acids in a target-specific manner. Though ionizing LNPs are in their early stages, they face several challenges, including only hepatic delivery, a short shelf life, and ultra-cold storage. In our opinion, ligand-based, target-specific synthesized novel lipids and advanced manufacturing technologies can easily overcome the restrictions and open up a new approach for improved therapeutic efficacy for chronic disorders. Graphical abstract
核酸电离脂质纳米粒子的故事:设计和制造技术和进步。
简介:可电离脂质纳米颗粒(LNPs)已被证明具有高包封性、细胞摄取性和有效的内体逃逸性,因此有望用于核酸递送。可电离脂类、辅助脂类、胆固醇和聚乙二醇脂类的结合促进了核酸可电离LNPs,并将其与脂质体、sln、NLCs和其他脂质颗粒区分开来。溶剂注入技术和微流体技术是可电离LNPs商业化的主要制造技术。微流体技术的局限性限制了电离LNPs的快速工业规模和治疗效果。迫切需要替代制造技术和目标特异性脂质。涉及领域:本文提供了核酸电离LNPs的脂质组成、临床试验和制造技术的深入更新。我们第一次更新了可电离LNPs和其他脂质颗粒之间的区别。我们还提出了一种替代的热循环技术,用于高工业规模和核酸电离LNPs的稳定性。专家意见:核酸电离LNPs在以特定靶标的方式递送核酸方面具有广阔的前景。虽然电离LNPs还处于早期阶段,但它们面临着一些挑战,包括只能通过肝脏输送、保质期短和超低温储存。我们认为,基于配体的、靶向性的合成新型脂质和先进的制造技术可以很容易地克服这些限制,为提高慢性疾病的治疗效果开辟一条新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
11.10
自引率
3.00%
发文量
104
审稿时长
3 months
期刊介绍: Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
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