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Pharmaceutics
Special Issues
Impact of Lipid Nanoparticle Physicochemical Properties on mRNA Vaccine
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Impact of Lipid Nanoparticle Physicochemical Properties on mRNA Vaccine

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 197

Special Issue Editor

Prof. Dr. Chuanxu Yang

E-Mail Website
Guest Editor
School of Chemistry and Chemical Engineering, Shandong University, Jinan 250199, China
Interests: biomaterials; drug delivery; gene therapy; nanomedicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As mRNA vaccines extend their applications from infectious diseases to oncology and other therapeutic areas, optimizing lipid nanoparticle (LNP) formulations is critical to enhancing vaccine efficacy, stability, and safety. Key physicochemical properties of LNPs—including lipid structure, particle size, surface charge, lipid composition, and structural characteristics—significantly influence mRNA delivery efficiency and immune response activation. A comprehensive understanding of how these properties affect mRNA delivery, biodistribution, and cellular uptake will facilitate advancements in vaccine design, formulation, and production. This special issue seeks to consolidate leading research and reviews examining the relationship between LNP physicochemical properties and mRNA vaccine performance. We invite original research articles, reviews, and perspectives on a variety of topics, including but not limited to: emerging technologies in LNP design, physicochemical property optimization, structure-function relationships, stability and storage solutions, targeted delivery and biodistribution, and safety and biocompatibility.

We look forward to receiving your contributions.

Prof. Dr. Chuanxu Yang
Guest Editor

Manuscript Submission Information

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Keywords

  • lipid nanoparticle formulation
  • ionizable lipids design
  • delivery of mRNA vaccines
  • sustained/controlled release
  • targeted delivery
  • stability and storage solutions
  • pharmacokinetics and pharmacodynamics

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Published Papers (1 paper)

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Research

16 pages, 4826 KiB  
Article
Formulation-Driven Optimization of PEG-Lipid Content in Lipid Nanoparticles for Enhanced mRNA Delivery In Vitro and In Vivo
by Wei Liu, Meihui Zhang, Huiyuan Lv and Chuanxu Yang
Pharmaceutics 2025, 17(8), 950; https://doi.org/10.3390/pharmaceutics17080950 (registering DOI) - 22 Jul 2025
Abstract
Background: Lipid nanoparticles (LNPs) represent one of the most effective non-viral vectors for nucleic acid delivery and have demonstrated clinical success in siRNA therapies and mRNA vaccines. While considerable research has focused on optimizing ionizable lipids and helper lipids, the impact of [...] Read more.
Background: Lipid nanoparticles (LNPs) represent one of the most effective non-viral vectors for nucleic acid delivery and have demonstrated clinical success in siRNA therapies and mRNA vaccines. While considerable research has focused on optimizing ionizable lipids and helper lipids, the impact of PEGylated lipid content on LNP-mediated mRNA delivery, especially in terms of in vitro transfection efficiency and in vivo performance, remains insufficiently understood. Methods: In this study, LNPs were formulated using a self-synthesized ionizable lipid and varying molar ratios of DMG-PEG2000. Nanoparticles were prepared via nanoprecipitation, and their physicochemical properties, mRNA encapsulation efficiency, cellular uptake, and transfection efficiency were evaluated in HeLa and DC2.4 cells. In vivo delivery efficiency and organ distribution were assessed in mice following intravenous administration. Results: The PEGylated lipid content exerted a significant influence on both the in vitro and in vivo performance of LNPs. A bell-shaped relationship between PEG content and transfection efficiency was observed: 1.5% DMG-PEG2000 yielded optimal mRNA transfection in vitro, while 5% DMG-PEG2000 resulted in the highest transgene expression in vivo. This discrepancy in optimal PEG content may be attributed to the trade-off between cellular uptake and systemic circulation: lower PEG levels enhance cellular internalization, whereas higher PEG levels improve stability and in vivo bioavailability at the expense of cellular entry. Furthermore, varying the PEG-lipid content enabled the partial modulation of organ distribution, offering a formulation-based strategy to influence biodistribution without altering the ionizable lipid structure. Conclusions: This study highlights the critical role of PEGylated lipid content in balancing nanoparticle stability, cellular uptake, and in vivo delivery performance. Our findings provide valuable mechanistic insights and suggest a straightforward formulation-based strategy to optimize LNP/mRNA systems for therapeutic applications. Full article
(This article belongs to the Special Issue Impact of Lipid Nanoparticle Physicochemical Properties on mRNA Vaccine)
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