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Optimizing mucosal vaccination: Exploiting Lactobionic acid-modified chitosan for superior gene delivery systems.

Mariana Colaço¹, João Panão-Costa¹, Maria T Cruz¹

¹CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-504, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, 3004-504, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, 3000-548, Portugal.

International Journal of Biological Macromolecules

|September 7, 2025

Summary

Researchers developed a novel lactobionic acid-functionalized chitosan platform for enhanced mucosal vaccine delivery. This platform improves antigen delivery and immune response, offering a promising solution for respiratory disorders.

Keywords:

Chitosan-based gene delivery Galactose receptors Polyplexes

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Area of Science:

Biomaterials Science
Vaccinology
Immunology

Background:

Rising respiratory disorders necessitate effective mucosal vaccines targeting pathogen entry sites.
Mucosal vaccine development faces hurdles in antigen delivery and overcoming immune tolerance.

Purpose of the Study:

To engineer a gene delivery system using lactobionic acid-functionalized chitosan for enhanced mucosal vaccine applications.
To evaluate the targeting, transfection efficiency, and immunomodulatory potential of the developed platform.

Main Methods:

Chitosan was functionalized with lactobionic acid (LA) and characterized using ATR-FTIR, NMR, and ninhydrin assays.
DNA polyplexes were formed with the modified chitosan and luciferase plasmid, with and without laminarin (LAM) adjuvant.
Transfection efficiency was assessed in A549 cells, and receptor-specific uptake was confirmed in HepG2 cells via ROS production.
Immunostimulatory effects were evaluated in human dendritic cells by measuring maturation markers and cytokine secretion (TNF-α, IL-12).

Main Results:

Successful functionalization of chitosan with LA was confirmed, leading to stable DNA polyplexes.
Polyplexes significantly enhanced transfection efficiency in A549 cells.
Receptor-specific uptake was demonstrated in HepG2 cells through ASGPR-mediated pathways.
The 7.5:1 LAM25 formulation showed potent immunostimulatory effects in dendritic cells, increasing maturation markers and pro-inflammatory cytokine secretion.

Conclusions:

Lactobionic acid-modified chitosan serves as a versatile platform for gene delivery in mucosal vaccine development.
The platform enhances antigen-presenting cell targeting and promotes robust immune responses.
This approach holds significant promise for creating effective next-generation mucosal vaccines against respiratory pathogens.