Microneedle patch-based delivery of mRNA vaccines: opportunities for next-generation immunization

Abstract Recent advances in messenger RNA (mRNA) vaccine technologies have enabled rapid responses to emerging infectious diseases and accelerated translation from antigen design to clinical deployment; however, their widespread implementation remains constrained by formulation instability, cold-chain dependence, multi-dose adherence challenges, and limited mechanisms for reliable verification of administration. These barriers reflect product-level and systems-level limitations rather than intrinsic deficiencies in mRNA efficacy, motivating the development of integrated delivery platforms that couple stability, dosing control, and verification within a single pharmaceutical product. Microneedle patch technologies address these challenges by combining intradermal delivery with solid-state formulation, stabilizing lipid nanoparticle (LNP)-encapsulated mRNA in dry matrices and enabling minimally invasive access to immunologically active skin layers, thereby reducing reliance on injection technique and cold-chain logistics. Advances in microneedle design and fabrication further enable spatial and temporal control of material deposition in the skin, supporting programmable release profiles, such as single-administration prime-boost strategies, as well as passive intradermal encoding of vaccination records. This review examines the design principles, formulation strategies, and translational considerations underlying microneedle patch-based delivery of mRNA vaccines, with a focus on dissolving and stimuli-responsive systems compatible with LNP formulations, mechanisms of intradermal transport and immune activation, solid-state stabilization approaches that preserve mRNA integrity, and emerging methods for embedding optically readable markers to enable administration verification independent of external records. Manufacturing scalability, quality control, and regulatory considerations are also discussed, emphasizing the need to treat formulation and fabrication as coupled design variables, and positioning microneedle patches as integrated vaccine products whose real-world performance is determined by the interplay of formulation, delivery, and manufacturing decisions.