Endosomal escape and current obstacles in ionizable lipid nanoparticles mediated gene delivery: lessons from COVID-19 vaccines.

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics Pub Date : 2025-10-10 DOI:10.1016/j.ijpharm.2025.126263

Semmal Syed Meerasa, Aqeel Ahmad, Amer Ali Khan, Shafiul Haque, Imran Saleem

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Abstract

During last pandemic of COVID-19, two vaccines based on ionizable lipid nanoparticles (ILNP) were developed for COVID-19 prevention: Pfizer/BioNTech Vaccine (BNT162b2) and Moderna Vaccine (mRNA-1273). The observed efficacy of these two vaccine formulations catalyzed a global intensification of scientific inquiry into the therapeutic potential of these ionizable lipids, driving research efforts aimed at developing novel agents for a diverse range of pathologies. Successful ILNP-based delivery requires both selection of a suitable ionizable lipid and elucidation of its endosomal escape mechanism. This review focuses current knowledge on lipid diversity, emphasizing the structural and functional attributes of ionizable lipids essential for endosomal escape. A detailed analysis of COVID-19 vaccine lipid components, correlating their physicochemical properties with cellular and humoral immune responses, and exploring their implications for therapeutic innovation. Finally, we evaluate current challenges and future directions in ILNP-based therapy development.

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可电离脂质纳米颗粒介导的基因递送中的内体逃逸和当前障碍：来自COVID-19疫苗的经验教训

在上次COVID-19大流行期间，基于电离脂质纳米颗粒（ILNP）的两种疫苗被开发用于预防COVID-19：辉瑞/BioNTech疫苗（BNT162b2）和Moderna疫苗（mRNA-1273）。观察到的这两种疫苗配方的功效，催化了对这些可电离脂质治疗潜力的全球科学探究的加强，推动了旨在开发针对各种病理的新型药物的研究工作。成功的基于ilnp的递送需要选择合适的可电离脂质和阐明其内体逃逸机制。本文综述了目前关于脂质多样性的知识，强调了内体逃逸所必需的可电离脂质的结构和功能属性。详细分析COVID-19疫苗脂质成分，将其理化性质与细胞和体液免疫反应相关联，并探索其对治疗创新的影响。最后，我们评估了当前的挑战和未来的方向，基于ilnp的治疗发展。

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

International Journal of Pharmaceutics 医学-药学

CiteScore

10.70

自引率

8.60%

发文量

951

审稿时长

72 days

期刊介绍： The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.