Impact-insertion applicator improves reliability of skin penetration by solid microneedle arrays.

Abstract

Microneedles are needle-like structures shorter than 1 mm that have been advocated as devices for enabling potentially pain-free intradermal delivery of biomacromolecules (1–5). To permit a reproducible delivery of the drug, microneedles should be inserted into the skin in a controlled and reproducible manner (4,6). Obviously, one of the factors that influence the penetration ability of microneedles is the insertion process itself, e.g., microneedles can be inserted manually or by using insertion devices (3,4,6–9). Recently, the penetration ability of low-density arrays (42 microneedles/cm2) with 750-μm long microneedles, applied manually or by using a snap-based applicator, was investigated (10). However, no studies have been reported on the efficiency and reproducibility of the insertion of high-density microneedles into human skin. Therefore, the aim of this study was to investigate the effect of the type of application on inter and intra individual variability of microneedle insertion into human skin by microneedle users. We show that participants using an impact-insertion applicator inserted high-density microneedles into ex vivo human skin with high efficiency and with a low inter and intra individual variation. However, when the same microneedle arrays were inserted by using a manual insertion device, the penetration efficiency was reduced by approximately 40% with a considerably lower reproducibility. Finally, the applicability of an impact-insertion applicator/microneedle array was confirmed in a vaccination study in mice.