Site-selectively coated, densely-packed microprojection array patches for targeted delivery of vaccines to skin

Abstract

Densely packed dry-coated microprojections are shown to deliver vaccines to targeted locations within the skin that are rich in immune cells, thus inducing protective immune responses against a lethal virus challenge. Selectively limiting the antigen coating to the tips of the projections, which penetrate the skin, would significantly reduce the amount of vaccine required in immunization. In this paper a simple technique, dip-coating the microprojections, is introduced to meet this goal. By increasing the coating solution viscosity, an otherwise strong capillary action is mitigated and the desired controlled coating length on projections is achieved. Following application to the skin, most of the coated vaccine material is rapidly released from the projections (82.6% in mass within 2 min) to the target locations within the skin strata and a potent immune response is induced when a conventional influenza vaccine (Fluvax) is tested in a mouse model. The utility of this coating approach to a variety of molecules representative of vaccines (e.g., chicken egg ovalbumin (OVA) protein, DNA, and fluorescent dyes) is demonstrated. These collective attributes, together with the simplicity of the approach, position the dip-coating method for practical utility in large vaccination campaigns. Densely packed microprojection arrays are site-selectively coated by dipping them in a solution of high viscosity. This technique provides microprojection arrays with desired coating attributes for vaccine delivery. It is universal for a wide range of molecules, provides quick release in skin, has high delivery efficiency, has the ability to induce potent immune responses, and is simple making it suitable for mass production. Show more