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Meerasa, SS, Ahmad, A, Khan, AA, Haque, S and Saleem, I 
ORCID: 0000-0003-2382-6668
(2025)
Endosomal escape and current obstacles in ionizable lipid nanoparticles mediated gene delivery: lessons from COVID-19 vaccines.
International Journal of Pharmaceutics.
p. 126263.
ISSN 0378-5173
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 3206 Medical Biotechnology; 32 Biomedical and Clinical Sciences; Nanotechnology; Bioengineering; Biotechnology; Vaccine Related; Coronaviruses Vaccines; Prevention; Emerging Infectious Diseases; Coronaviruses; Infectious Diseases; Immunization; 3.4 Vaccines; 3 Good Health and Well Being; 1115 Pharmacology and Pharmaceutical Sciences; Pharmacology & Pharmacy; 3214 Pharmacology and pharmaceutical sciences |
| Subjects: | R Medicine > RS Pharmacy and materia medica |
| Divisions: | Pharmacy and Biomolecular Sciences |
| Publisher: | Elsevier |
| Date of acceptance: | 7 October 2025 |
| Date of first compliant Open Access: | 21 October 2025 |
| Date Deposited: | 21 Oct 2025 09:16 |
| Last Modified: | 21 Oct 2025 09:30 |
| DOI or ID number: | 10.1016/j.ijpharm.2025.126263 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/27390 |
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