Chemoattractant releasing microneedles for enhanced DNA vaccination

Transcutaneous delivery of a DNA vaccine using microneedle (MN) has attracted much attention since there are a variety of immune cells underneath the skin. However, the clinical use of DNA vaccine is limited due to its poor cellular uptake of naked plasmid DNA (pDNA) and suboptimal presentation of an antigen by antigen presenting cells (APC). Herein, we designed a MN system for delivering polyplex-based DNA vaccine and recruiting APCs by a chemoattractant N-formyl-methionyl-leucyl-phenylalanine peptide (fMLP)-releasing microspheres (fMLP-MS) using MN coated with pH-responsive polyelectrolyte multilayer assembly (PMA). The PMA can be rapidly disrupted upon the application of MN to the skin, leading to the release of polyplex and fMLP-MS. The polyplex would be taken up by the epidermal cells and resident APCs to express and secrete the antigen (amyloid beta monomer, Aβ_1-42) encoded in the DNA vaccine. fMLP released from fMLP-MS could recruit APCs to the site of MN administration by chemotactic effects. The MN-based vaccination system was able to induce robust antigen-specific antibody production.