Iontophoresis-Driven Microneedles Patch for Active Transdermal Delivery of Vaccine Macromolecules

Abstract

Abstract COVID-19 has seriously threatened public health and transdermal vaccination is an effective way to prevent pathogen infection. Microneedles (MN) can damage the stratum corneum for passive diffusion of vaccine macromolecules but the delivery efficiency is low, while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of stratum corneum. Herein, we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and efficient transdermal vaccine macromolecules delivery. Polyacrylamide/chitosan hydrogels with good biocompatibility, excellent conductivity, high elasticity and large loading capacity were prepared as the key component for vaccine storage and active iontophoresis. The transdermal vaccine delivery strategy of the iontophoresis-driven MN patch is: “press and poke, iontophoresis-driven delivery, and immune response”. We demonstrated that the synergistic effect of MN puncture and iontophoresis could significantly promote the transdermal vaccine delivery efficiency. In vitro experiments showed that the transdermal delivery amount of ovalbumin using iontophoresis-driven MN patch could be controlled by the iontophoresis current. In vivo immunization studies of Balb/c mice demonstrated that transdermal inoculation of ovalbumin using iontophoresis-driven MN patch induced an effective immune response, which was even stronger than that traditional intramuscular injection. Moreover, the iontophoresis-driven MN patch had little biosafety concern. This delivery system is low-cost, user-friendly, and active delivery that shows a great potential in vaccine self-administration at home.