Maltodextrin-modified lipoplexes for enhanced mucosal penetration and efficient mRNA delivery.

Area of Science:

• Biotechnology
• Nanotechnology
• Gene Therapy

Background:

• Efficient messenger ribonucleic acid (mRNA) delivery to mucosal tissues is crucial for localized protein production.
• Current methods face challenges in penetrating the mucus layer of the nasal and respiratory tract.

Purpose of the Study:

• To investigate maltodextrin (MDX) as a surface modifier for enhancing mRNA-loaded histidylated lipoplexes (LXs) delivery to airway epithelial cells.
• To evaluate the impact of MDX on mRNA delivery, cellular uptake, and protein expression both in vitro and in vivo.

Main Methods:

• Formulation of mRNA-loaded lipoplexes (LXs) with and without MDX surface modification.
• In vitro assessment of cellular uptake, transfection efficiency, and protein expression in airway epithelial cells.
• In vivo evaluation of gene expression following intranasal administration of MDX-modified LXs.

Main Results:

• MDX coating reduced lipoplex hydrophobicity, improving mucus penetration and cellular uptake.
• MDX-coated LXs demonstrated a four-fold increase in transfection efficiency and sustained protein expression up to 48 hours in vitro.
• Intranasal administration of MDX-LXs resulted in efficient gene expression in vivo.

Conclusions:

• Maltodextrin is a promising surface modifier for enhancing mRNA lipoplex delivery to the nasal and respiratory tract.
• MDX integration improves mRNA delivery efficiency, cellular uptake, and gene expression for potential therapeutic applications.
• This approach offers a viable strategy for advancing nasal gene therapy and protein replacement applications.