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The buccal mucosa (inner cheek) is an attractive site for delivery of immunotherapeutics, due to its ease of access and rich antigen presenting cell (APC) distribution. However, to date, most delivery methods to the buccal mucosa have only been topical—with the challenges of: 1) an environment where significant biomolecule degradation may occur; 2) inability to reach the APCs that are located deep in the epithelium and lamina propria; and 3) salivary flow and mucous secretion that may result in removal of the therapeutic agent before absorption has taken place. To overcome these challenges and achieve consistent, repeatable targeted delivery of immunotherapeutics to within the buccal mucosa (not merely on to the surface), we utilised microprojection arrays (Nanopatches—110 μm length projections, 3364 projections, 16 mm2 surface area) with a purpose built clip applicator. The mechanical application of Nanopatches bearing a dry-coated vaccine (commercial influenza vaccine, as a test case immunotherapeutic) released the vaccine to a depth of 47.8 ± 14.8 μm (mean ± SD, n = 4), in the mouse buccal mucosa (measured using fluorescent delivered dyes and CryoSEM). This location is in the direct vicinity of APCs, facilitating antigenic uptake. Resultant systemic immune responses were similar to systemic immunization methods, and superior to comparative orally immunised mice. This confirms the Nanopatch administered vaccine was delivered into the buccal mucosa and not ingested. This study demonstrates a minimally-invasive delivery device with rapid (2 min of application time), accurate and consistent release of immunotherapeutics in to the buccal mucosa—that conceptually can be extended in to human use for broad and practical utility.