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

mRNA therapy holds promise for treating a variety of diseases, but its clinical application faces significant challenges, including rapid degradation in vivo and the need for frequent injections. Lipid nanoparticles (LNPs) are currently the clinically advanced delivery system for mRNA, yet issues such as short half-life and burst release after injection hinder their effectiveness. In this study, we developed a microcapsule-based system using polycaprolactone (PCL) to encapsulate mRNA LNPs, aiming to improve their stability, prolong in vivo retention, and enable sustained release. Microcapsules were fabricated using a customized microfluidic approach, resulting in uniform microcapsules with precise control over size and shell thickness. In vitro release studies showed that these microcapsules provided effective protection for mRNA LNPs and controlled their release over extended periods. In vivo studies demonstrated that mRNA LNP-loaded microcapsules significantly extended the retention time of mRNA in mice, maintaining mRNA expression for up to 8 days following a single injection. These findings highlight the potential of this microcapsule-based delivery system for long-lasting mRNA delivery, improving both therapeutic efficacy and patient compliance.