The Use of a Pressure-Indicating Sensor Film to Provide Feedback upon Hydrogel-Forming Microneedle Array Self-Application In Vivo

Abstract

PurposeTo evaluate the combination of a pressure-indicating sensor film with hydrogel-forming microneedle arrays, as a method of feedback to confirm MN insertion in vivo.MethodsPilot in vitro insertion studies were conducted using a Texture Analyser to insert MN arrays, coupled with a pressure-indicating sensor film, at varying forces into excised neonatal porcine skin. In vivo studies involved twenty human volunteers, who self-applied two hydrogel-forming MN arrays, one with a pressure-indicating sensor film incorporated and one without. Optical coherence tomography was employed to measure the resulting penetration depth and colorimetric analysis to investigate the associated colour change of the pressure-indicating sensor film.ResultsMicroneedle insertion was achieved in vitro at three different forces, demonstrating the colour change of the pressure-indicating sensor film upon application of increasing pressure. When self-applied in vivo, there was no significant difference in the microneedle penetration depth resulting from each type of array, with a mean depth of 237 μm recorded. When the pressure-indicating sensor film was present, a colour change occurred upon each application, providing evidence of insertion.ConclusionsFor the first time, this study shows how the incorporation of a simple, low-cost pressure-indicating sensor film can indicate microneedle insertion in vitro and in vivo, providing visual feedback to assure the user of correct application. Such a strategy may enhance usability of a microneedle device and, hence, assist in the future translation of the technology to widespread clinical use.

Successful application of large microneedle patches by human volunteers

“…While the earliest work was rightly centred on the fundamental science of delivery and understanding of the resulting physiological effects, recent years have seen enhanced emphasis on translation to patient benefit and commercial return, with several notable companies making progress towards commercialisation. Indeed, a number of studies examining patient usability (Birchall et al, 2011, Donnelly et al, 2014a, Vicente-Pérez et al, 2016), scaled-up manufacture and quality control testing (Larrañeta et al, 2015, Larrañeta et al, 2016b, Lutton et al, 2015b), sterile production (McCrudden et al, 2015a) and regulatory considerations (Lutton et al, 2015a) have now been published. MN with applications in improving skin appearance are now available commercially, though it is notable that these are not approved drug products (McCrudden et al, 2015b).…”

“…To date, MN have been inserted into skin manually, or by using an applicator device (Singh et al, 2011, Vicente-Pérez et al, 2016). Such approaches work relatively well for small patches, as the applied force is easily focused over a small area.…”

“…Before the volunteers applied the patches, baseline transepidermal water loss (TEWL) values were recorded at the edge of where the patch was to be applied and at the centre by carefully resting the TEWL probe (VapoMeter ® , Delfin Technologies Ltd, Kuopio, Finland) on the application site, with the probe head vertical and perpendicular to the skin, to give an indication of skin barrier function. TEWL measures the outward diffusion of water through the skin and, as such, provides information on the barrier status (Vicente-Pérez et al, 2016). Measurement of TEWL is often used as an alternative to invasive measures of skin barrier integrity obtained by local excision or biopsy.…”

Novel nanosuspension‐based dissolving microneedle arrays for transdermal delivery of a hydrophobic drug

“…MNs are minimally invasive, pain‐free, micron‐sized projection arrays (10 μm −900 μm) on baseplates capable of piercing the skin's stratum corneum , overcoming its barrier properties to create a transport pathway for drug molecules. MN has been shown to be suitable for self‐administration by patients (Kaushik et al, ; Prausnitz, ; Vicente‐Prez et al, ). A vast array of different MN types have been studied, including solid MN (Henry, McAllister, Allen, & Prausnitz, ), drug‐coated MN (McGrath et al, ), and dissolving MN (DMN).…”

Advances in the Design of Transdermal Microneedles for Diagnostic and Monitoring Applications

“…Despite their reliability, the inclusion of an applicator device with each MN array could greatly increase the cost of commercial translation. To overcome this issue, novel methods have been explored for improving the reproducibility of the manual insertion of MNs, notably through the inclusion of a pressure‐sensitive film on the back of each MN array . By attaching this membrane, which displays a color‐change when pressure sufficient to breach the stratum corneum is applied to the MNs, a visual assurance is provided to users that the MNs have been correctly inserted.…”