resumo
Efficient delivery of messenger ribonucleic acid (mRNA) to mucosal tissues represents a promising approach for localized protein production in the nasal and respiratory tract. Here, we investigate the use of maltodextrin (MDX) as a surface modifier to enhance the delivery of mRNA-loaded histidylated lipoplexes (LXs) to airway epithelial cells. By reducing hydrophobicity, MDX facilitates better penetration through the mucus layer, enabling effective mRNA delivery. MDX-coated LXs improve mRNA delivery and expression in vitro by increasing cellular uptake and supporting sustained protein production. Additionally, MDX incorporation stabilizes inhouse-formulated lipoplexes and modulates their interactions with mucin-covered cells. Notably, MDX-coated mRNA LXs display a four-fold increased transfection efficiency, and the protein expression is maintained up to 48 h post-transfection. Furthermore, intranasal administration of MDX-LXs results in efficient gene expression in vivo. Overall, our findings reveal that integrating MDX into mRNA lipoplexes is a promising strategy to advance nasal delivery for gene therapy and protein replacement applications.
palavras-chave
TRANSFECTION; VACCINES; MUCUS
categoria
Engineering; Materials Science
autores
Kopilovic, B; Laroui, N; Berchel, M; Midoux, P; Freire, MG; Pichon, C
nossos autores
Bojan Kopilovic
Estudante de doutoramento
Mara Guadalupe Freire Martins
Professor CatedráticoProjectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
agradecimentos
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.54499/UIDB/50011/2020) , UIDP/50011/2020 (DOI 10.54499/UIDP/50011/2020) & LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020) , financed by national funds through the FCT/MCTES (PIDDAC) . This work was developed within the scope of the EIC-Pathfinder YSCRIPT project with reference 101047214, supported by the budgets of the Horizon Europe Program. Bojan Kopilovic acknowledges the FCT for the PhD grant DOI 10.54499/2020.06481.BD. Chantal Pichon acknowledges Ligue National contre le cancer and ANR France 2030 PEPR Biotherapies and Bioproduction of innovatives therapies for their financial supports.