ArticleVaccines2025
Exploring the Challenges of Lipid Nanoparticle Development: The In Vitro-In Vivo Correlation Gap.
Article in Vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Elucidating lipid nanoparticle properties and structure through biophysical analyses.Nature biotechnology · 2026Article
- Lipid Nanoparticle Co-Delivery of mRNA and a Small Molecule Drug for Oral Cancer Chemoimmunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Multiscale modeling guided potency assessment of mRNA-lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- Delivery of Monomethyl Auristatin E Using Ionizable Lipid Nanoparticles for B‑Cell Acute Lymphoblastic Leukemia Treatment.ACS omega · 2026Article
- Nanostructured Lipid Carriers Enable In Vivo Efficacy of Parthenolide inPharmaceutics · 2026Article
- Lipid Nanoparticle Surface Engineering with Heparosan Polysaccharides for Safe and Effective mRNA DeliveryACS applied materials & interfaces · 2026Article
- Effects of different mixing techniques on mRNA lipid nanoparticle physicochemistry and biological performance.Nature communications · 2026Article
- Functionalized Lipid Nanoparticles for Targeted RNA Delivery in Immune and Inflammatory Diseases.Biomedicines · 2026Review
- Industrial Perspective on the Manufacturing of Lipid Nanoparticles for Nucleic Acid Delivery.Pharmaceutics · 2026Review
- Functional Reclassification of Lipid-Based Drug Delivery Systems and Advances in Formulation Strategies and Manufacturing Challenges.AAPS PharmSciTech · 2026Review
- Deciphering the biological fate of mRNA-LNP-based biologics: A perspective from tissue to intracellular distribution.Acta pharmaceutica Sinica. B · 2026Review
- Programmable lipid nanoparticles for RNA therapeutics: Design principles and clinical translation.Materials today. Bio · 2026Review
- Spleen-targeted mRNA delivery via long-chain PEGylated lipids at low molar ratio enhances antitumor immunity against melanoma.Molecular therapy. Nucleic acids · 2026Article
- Overcoming delivery barriers of large all-in-one CRISPR/Cas9 plasmids using lysine-based lipid nanoparticles.Frontiers in genome editing · 2026Article
- A Comprehensive Dataset of Lipid Nanoparticle Compositions and Properties for Nucleic Acid Delivery.Scientific data · 2025Article
- Design of cationic ionizable lipids for the delivery of therapeutic nucleic acids.Molecular therapy. Methods & clinical development · 2025Review
- Enhancing pharmacokinetic properties of Chikusetsusaponin IVa via modification of polyethylenimine/poly(lactic-co-glycolic acid) nanoparticles for sustained drug delivery.Scientific reports · 2025Article
- Lipid nanoparticle co-delivery of mRNA and a small molecule drug for oral cancer chemoimmunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Elucidating lipid nanoparticle properties and structure through biophysical analyses.bioRxiv : the preprint server for biology · 2025Article
- Cost-Effective and Reproducible Preparation of mRNA-Loaded Lipid Nanoparticles Using a Conventional Laboratory-Scale Microfluidic Assembly System.Bio-protocol · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
objectivesThe development of lipid nanoparticles (LNPs) as delivery platforms for nucleic acids has revolutionised possibilities for both therapeutic and vaccine applications. However, emerging studies highlight challenges in achieving reliable in vitro-in vivo correlation (IVIVC), which delays the translation of experimental findings into clinical applications. This study investigates these potential discrepancies by evaluating the physicochemical properties, in vitro efficacy (across three commonly used cell lines), and in vivo performance (mRNA expression and vaccine efficacy) of four LNP formulations.
methodsLNPs composed of DSPC, cholesterol, a PEGylated lipid, and one of four ionizable lipids (SM-102, ALC-0315, MC3, or C12-200) were manufactured using microfluidics.
resultsAll formulations exhibited comparable physicochemical properties, as expected (size 70-100 nm, low PDI, near-neutral zeta potential, and high mRNA encapsulation). In vitro studies demonstrated variable LNP-mediated mRNA expression in both immortalised and immune cells, with SM-102 inducing significantly higher protein expression (
conclusionsThese findings highlight the complexities of correlating in vitro and in vivo outcomes in LNP development and demonstrate the importance of holistic evaluation strategies to optimise their clinical translation.
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