Microneedle-mediated intradermal delivery of mRNA-loaded silica nanoparticles for thermostable mRNA delivery

초록

Messenger RNA (mRNA)-based therapeutics have emerged as a promising platform owing to their rapid development, design flexibility, and scalable manufacturing potential. However, the inherent instability of mRNA and the need for thermostable, high-capacity delivery systems remain major barriers to clinical translation. Herein, we report a high-dose coated microneedle (MN) platform based on contact dispensing coating (CDC), employing polyethyleneimine-coated silica nanoparticles (PSiNPs) as a high-capacity mRNA carrier to achieve nanoliter-level coating precision, accurate dose control, and enhanced mRNA stability. PSiNPs efficiently complexed with mRNA through electrostatic interactions, and an optimized PSiNP-to-mRNA ratio of 10:1 provided high encapsulation efficiency with low cytotoxicity and effective intracellular delivery. The CDC process enabled precise tip-selective coating, with the coating amount increasing linearly with the number of coating cycles. Among the evaluated coating formulations, polyvinylpyrrolidone-based formulations showed superior coating uniformity, dispersion stability, and intradermal delivery efficiency. Ex vivo and in vivo studies demonstrated efficient skin penetration, successful intradermal delivery of mRNA-loaded PSiNPs, and robust mCherry protein expression following MN application. This PSiNP-coated MN platform provides accurate dose control, improved formulation stability, and reduced dependence on cold-chain storage, offering a promising transdermal delivery strategy for next-generation mRNA vaccines and nucleic acid therapeutics.

키워드