TY - JOUR
T1 - Endosomal escape and current obstacles in ionizable lipid nanoparticles mediated gene delivery
T2 - lessons from COVID-19 vaccines
AU - Meerasa, Semmal Syed
AU - Ahmad, Aqeel
AU - Khan, Amer Ali
AU - Haque, Shafiul
AU - Saleem, Imran
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/11/30
Y1 - 2025/11/30
N2 - 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.
AB - 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.
KW - COVID-19 vaccines
KW - Endosomal escape
KW - Gene/RNA delivery
KW - Ionizable Lipid Nanoparticles
KW - Types of ionizable lipid
UR - https://www.scopus.com/pages/publications/105018662024
U2 - 10.1016/j.ijpharm.2025.126263
DO - 10.1016/j.ijpharm.2025.126263
M3 - Artículo de revisión
C2 - 41077088
AN - SCOPUS:105018662024
SN - 0378-5173
VL - 685
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 126263
ER -
