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.

Microneedle‐Mediated Transcutaneous Immunization: Potential in Nucleic Acid Vaccination

“…A few applicators may help promote the translation of dissolvable MNs. For instance, Kim et al [113] fabricated a film-trigger applicator (FTA) composed of CMC film and micropillars to deliver dissolvable MNs into the skin using fracture energy of CMC film (Figure 6G). The applicator showed better delivery than traditional dissolvable MNs, and it worked with simple finger force without external equipment.…”

“…Reproduced with permission under the terms of the CC‐BY 4.0 license. [ 113 ] Copyright 2022, the Authors. Published by BioMed Central.…”

“…The applicator showed better delivery than traditional dissolvable MNs, and it worked with simple finger force without external equipment. [ 113 ] The FTA could be a promising applicator for dissolvable MNs and more tools like this are expected to be proposed to boost the clinical translation of dissolvable MNs.…”

“…G) The composition and application steps of the film-trigger applicator (FTA). Reproduced with permission under the terms of the CC-BY 4.0 license [113]. Copyright 2022, the Authors.…”

Transdermal drug delivery via microneedles for musculoskeletal systems

“…However, an enlarged patch can give rise to uneven force and incomplete insertion of needles, 50 which can be avoided by using an applicator to reduce the variability of TDD and raise the efficiency of insertion, 51,52 among which a film-trigger applicator (FTA) system has been developed to eliminate the complexity brought by the applicators. 51 Unlike others, this applicator can deliver the drug into the skin layer through micropillars using the energy of the carboxymethyl cellulose (CMC) film fracture, which may optimize the process of TDD in MSK diseases if introduced properly. Meanwhile, MNP with high density sometimes cause the ''bed of nails'' effect mainly due to the dispersed and weakened force during insertion.…”