Development of a dissolving microneedle patch for transdermal delivery of SARS-CoV-2 mRNA vaccine with enhanced stability and immunogenicity

Sep 26, 2025Journal of controlled release : official journal of the Controlled Release Society

Dissolving microneedle patch for skin delivery of a stable and effective COVID-19 mRNA vaccine

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Abstract

The dissolving microneedle patch (DMP) achieved a 95.54 ± 1.29% encapsulation efficiency of mRNA lipid nanoparticles (LNPs).

In vivo imaging showed the one-step DMP resulted in 2.2-fold higher cumulative fluorescence intensity compared to the two-step DMP.
The DMP exhibited 2.6-fold higher fluorescence intensity than intramuscular injection (IM) delivery of the vaccine.
Key physicochemical properties and biological functions of mRNA-LNPs were preserved in the DMP, allowing for effective cellular uptake and antigen expression.
The DMP maintained stability over 30 days at room temperature, showing no significant changes in key properties.
The DMP induced a comparable IgG response to IM delivery at a lower dosage of approximately 2 μg, with no observed systemic toxicity or skin irritation.

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Microneedles (MNs)-based transdermal delivery systems present a promising alternative to intramuscular injection (IM) for mRNA vaccines, offering improved patient compliance, enhanced skin-targeted delivery, and increased vaccine stability while reducing hepatic accumulation of lipid nanoparticles (LNPs). Here, we developed a dissolving microneedle patch (DMP) for SARS-CoV-2 mRNA vaccine RQ3013 delivery, employing a matrix composed of 15 % polyvinyl alcohol (PVA) and 10 % polyvinylpyrrolidone (PVP) for its optimal mechanical properties and mRNA-LNPs compatibility. We utilized the one-step vacuum micro-molding process to fabricate DMP loaded with mRNA-LNPs, which significantly improved the encapsulation efficiency of mRNA-LNPs in MNs from 72.34 ± 1.44 % (two-step vacuum micro-molding process) to 95.54 ± 1.29 %. In vivo imaging revealed that the one-step DMP achieved 2.2-fold higher cumulative fluorescence intensity than the two-step DMP and 2.6-fold higher than IM. The DMP preserved the key physicochemical properties and biological functions of mRNA-LNPs, enabling efficient cellular uptake and target antigen expression following successful endosomal escape. Remarkably, the DMP exhibited excellent stability, with no significant changes in key properties after 30 days of storage at room temperature. Notably, the DMP induced a comparable IgG response to IM (5 μg) at a substantially lower actual delivery dose (approximately 2 μg), without systemic toxicity or skin irritation. These findings demonstrate that this DMP represents an effective, stable, and patient-friendly strategy for mRNA vaccine delivery, combining enhanced immunogenicity with improved storage stability and simplified administration.

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Development of a dissolving microneedle patch for transdermal delivery of SARS-CoV-2 mRNA vaccine with enhanced stability and immunogenicity

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