Film-trigger applicator (FTA) for improved skin penetration of microneedle using punching force of carboxymethyl cellulose film acting as a microneedle applicator

Abstract

Background: Dissolving microneedle (DMN) is a transdermal drug delivery system that creates pore in the skin and directly deliver drug through the pore channel. DMN is considered as one of the promising system alternatives to injection because it is minimally invasive and free from needle-related issues. However, traditional DMN patch system has limitations of incomplete insertion and need of complex external devices. Here, we designed film-trigger applicator (FTA) system that successfully delivered DMN inside the skin layers using fracture energy of carboxymethyl cellulose (CMC) film via micropillars. We highlighted advantages of FTA system in DMN delivery compared with DMN patch, including that the film itself can act as DMN applicator. Methods: FTA system consists of DMNs fabricated on the CMC film, DMN array holder having holes aligned to DMN array, and micropillars prepared using general purpose polystyrene. We analyzed punching force on the film by micropillars until the film puncture point at different CMC film concentrations and micropillar diameters. We also compared drug delivery efficiency using rhodamine B fluorescence diffusion and skin penetration using optical coherence tomography (OCT) of FTA with those of conventional DMN patch. In vivo experiments were conducted to evaluate DMN delivery efficiency using C57BL/6 mice and insulin as a model drug. Results: FTA system showed enhanced delivery efficiency compared with that of the existing DMN patch system. We concluded CMC film as a successful DMN applicator as it showed enhanced DMN penetration in OCT and rhodamine B diffusion studies. Further, we applied FTA on shaved mouse dorsal skin and observed successful skin penetration. The FTA group showed higher level of plasma insulin in vivo than that of the DMN patch group. Conclusions: FTA system consisting of simple polymer film and micropillars showed enhanced DMN delivery than that of the existing DMN patch system. Because FTA works with simple finger force without sticky patch and external devices, FTA is a novel and promising platform to overcome the limitations of conventional microneedle patch delivery system; we suggest FTA as a next generation applicator for microneedle application in the future.