Precise microfluidic engineering of mRNA lipid nanoparticle-loaded polycaprolactone microcapsules for sustained...

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Molecular Therapeutics

Background:

• Messenger RNA (mRNA) therapy offers potential for treating various diseases.
• Clinical use of mRNA is limited by rapid degradation and frequent administration needs.
• Current lipid nanoparticle (LNP) delivery systems for mRNA have short half-lives and burst release issues.

Purpose of the Study:

• To develop a microcapsule-based system for encapsulating mRNA LNPs.
• To enhance mRNA LNP stability and prolong in vivo retention.
• To achieve sustained release of mRNA for improved therapeutic outcomes.

Main Methods:

• Fabrication of polycaprolactone (PCL) microcapsules using a microfluidic approach.
• Encapsulation of mRNA LNPs within PCL microcapsules.
• In vitro release studies to assess release kinetics.
• In vivo studies in mice to evaluate mRNA retention and expression.

Main Results:

• Uniform microcapsules with controlled size and shell thickness were produced.
• Microcapsules demonstrated effective protection of mRNA LNPs and sustained release in vitro.
• In vivo studies showed extended mRNA retention up to 8 days post-single injection in mice.
• Prolonged mRNA expression was maintained for up to 8 days.

Conclusions:

• The developed PCL microcapsule system offers a promising strategy for long-lasting mRNA delivery.
• This approach can improve mRNA therapeutic efficacy by ensuring sustained release and prolonged action.
• The system has the potential to enhance patient compliance through reduced injection frequency.