A Rapidly Dissolvable Microneedle Patch with Tip-Accumulated Antigens for Efficient Transdermal Vaccination

Dissolvable microneedles (DMNs) are an attractive alternative for vaccine delivery due to their user-friendly, skin-targeted, and minimally invasive features. However, vaccine waste and inaccurate dosage remain significant issues faced by DMNs, as the skin's elasticity makes it difficult to insert MNs completely. Here, a simple and reliable fabrication method are introduced based on two-casting micromolding with centrifugal drying to create a rapidly DMN patch made of hyaluronic acid. Ovalbumin (OVA), as the model antigens, is concentrated in the tip parts of the DMNs (60% of the needle height) to prevent antigen waste caused by skin elasticity. The time and temperature of the initial centrifugal drying significantly affect antigen distribution within the needle tips, with lower temperature facilitating antigen accumulation. The resulting DMN patch is able to penetrate the skin with enough mechanical strength and quickly release antigens into the skin tissue within 3 min. The in vivo study demonstrates that immunization of OVA with DMNs outperforms conventional vaccination routes, including subcutaneous and intramuscular injections, in eliciting both humoral and cellular immunity. This biocompatible DMN patch offers a promising and effective strategy for efficient and safe vaccination.