Purpose: mRNA vaccines have shown to be suitable for tackling emerging pandemics due to their rapid development process, superior efficacy, and favorable safety profile. A significant drawback of the currently marketed mRNA products is their low stability requiring storage at negative temperatures, implying challenges in their transport and distribution, while consequently increasing costs. Here, we embedded the novel mRNA-LNP in microneedle array patches (MAPs) and tested their long-term stability and in vivo potency.
Methods: For stability studies, we embedded mRNA-LNPs encoding for luciferase into MAPs, stored them under refrigerated, ambient, or elevated stress conditions (40°C) and compared with identical mRNA-LNP stored as liquids frozen at -80°C. The physicochemical properties of LNPs after drying were assessed by DLS, RiboGreen assay and RP-HPLC for measuring the integrity of mRNA and lipids. The in vitro transfection efficiency was measured in HeLa cells. For assessment of in vivo potency, mRNA-LNPs encoding the rabies virus glycoprotein were embedded in MAPs and guinea pigs were vaccinated twice at days 0 and 21. The virus neutralizing titers in serum were quantified at days 21 and 28.
Results: The optimal MAP candidates can be stored in the refrigerator with minimal change of physicochemical parameters and in vitro transfection efficiency for one year. At ambient and elevated stress conditions, MAPs showed complete hydrolysis of mRNA integrity and loss of transfection efficiency within 5 weeks. MAPs containing mRNA-LNP encoding the rabies virus glycoprotein produced relevant virus neutralizing titers after prime-boost vaccination of guinea pigs.
Conclusion: Presentation of mRNA in MAPs is a promising application strategy that might overcome stability issues and could help to increase opportunities for mRNA medicines on the post-pandemic pharmaceutical market. In addition, the needle-free application of mRNA via MAPs might increase patient compliance to vaccination and reduce needle-related side effects.
