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September 1, 2026European Journal of Lipid Science and Technology

Engineered Lipid Nanoparticles beyond mRNA Vaccines: Advances in Lipid Design, Protein Corona Dynamics, and Expanding Therapeutic Horizons

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Authors

TITaruna IkrarWMWachyudi MuchsinASAlfi Sophian

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Overview

Narrative review synthesizes advances in lipid nanoparticle engineering and protein corona biology for diverse diseases, highlighting strategies for extrahepatic delivery and clinical translation.

Key Points

  • To synthesize advances in lipid nanoparticle (LNP) engineering from 2019 to 2026 across lipid chemistry, biological interactions, and expanded clinical applications beyond mRNA vaccines.
  • Reviewed literature spanning 2019–2026 covering ionizable lipid architectures, biodegradable linkers, PEGylation alternatives, and AI-driven formulation platforms.
  • Assessed non-vaccine therapeutic applications including CRISPR-Cas9 genome editing, cancer immunotherapy, siRNA delivery, and central nervous system targeting from a regulatory science perspective.
  • Advanced lipid architectures and biodegradable linkages enhance endosomal escape, reduce tissue accumulation, and minimize immunogenic clearance.
  • Dynamic protein corona formation strongly dictates in vivo organ tropism and cellular uptake, serving as a primary determinant of nanoparticle clearance and biodistribution.
  • Critical translational challenges remain in achieving predictable extrahepatic delivery, establishing standardized protein corona analytical assays, and aligning global regulatory requirements.

Cite This Study

Ikrar et al. (2026) studied this question.

synapsesocial.com/papers/6aa916059f197399277103afhttps://doi.org/10.1002/ejlt.70143
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