Fig 1.
Schematic representation demonstrating the principle of MN-mediated TDM.
Images display swelling of hydrogel MN upon insertion due to ISF uptake, capture and extraction of analyte of interest and ultimately quantification of analyte.
Fig 2.
(A) Schematic representation of casting and crosslinking of hydrogel film formulations. (B) Diagrammatic representation of steps involved in the preparation of polymeric MNs. Polymer matrix was transferred to the silicone mould (i). The mould was centrifuged at 3000 rpm for 15 minutes (ii). Upon drying and heating for 24 h at 80°C to induce ester-based crosslinking, the silicone mould was carefully peeled away from the polymeric MN array and side walls removed using a hot scalpel blade (iii). Digital photograph image of MN with side walls (iv). Digital image of MN after removing the side walls using hot scalpel blade (v). (C) Illustration of the modified Franz cell apparatus used to investigate MN uptake of analytes across excised dermatomed neonatal porcine skin in vitro.
Fig 3.
Swollen MN arrays after removal from (A) the back of a rat and (B) the forearm of a human volunteer, both following 1 h insertion. OCT images showing MN inserted in the forearm of a human volunteer at t = 0 h (C) and in the swollen state after 1 h (D).
Fig 4.
(A) Quantities of theophylline (μg) taken up in vitro by MN arrays 5, 30 and 60 min after insertion into dermatomed excised neonatal porcine skin mounted on modified Franz cells and bathed on the underside by phosphate buffered saline pH 7.4 thermostated to 37°C and containing defined concentrations of theophylline (Means ± SD, n = 6). (B) Quantity of theophylline (μg) taken up in vivo by MN arrays inserted into the skin on the back of Sprague Dawley® rats for 1 h after administering theophylline via oral gavage at doses of 5 and 10 mg/kg of rat’s body mass (Means ± SD, n = 6). (C) Exemplar chromatogram showing HPLC detection of theophylline following extraction from MN after insertion into the skin on a rat’s back for 1 h. Dose administered to rat via oral gavage = 10 mg/kg. (D) Exemplar chromatogram showing HPLC detection of theophylline from a plasma sample obtained from a rat via lateral vein tail puncture 1 h after administration of theophylline (10 mg/kg) via oral gavage.
Fig 5.
(A) Quantity of caffeine (μg) taken up in vitro by MN arrays 5 and 60 min after insertion into dermatomed excised neonatal porcine skin mounted on modified Franz cells and bathed on the underside by phosphate buffered saline pH 7.4 thermostated to 37°C and containing defined concentrations of caffeine (Means ± SD, n = 6). (B) Comparison of caffeine (μg) detected in plasma versus levels detected from MN arrays inserted in the forearm of human volunteers at defined time points (0–1, 1–2, 2–3 and 0–3 h) following administration of defined caffeine doses (Mean ± SD, n = 9). (C) Exemplar chromatogram showing HPLC detection of caffeine following extraction from MN after insertion in the forearm of a human volunteer for 1 h. Dose administered = 100 mg oral caffeine in the form of two Proplus® tablets. (D) Exemplar chromatogram showing HPLC detection of caffeine from a plasma sample obtained from a human volunteer 1 h after the administration of 100 mg of caffeine. 7-BHT was used as an internal standard.
Fig 6.
(A) Quantity of glucose (μg) taken up in vitro by MN arrays 5 and 60 min after insertion into dermatomed excised neonatal porcine skin mounted on modified Franz cells and bathed on the underside by phosphate buffered saline pH 7.4 thermostated to 37°C and containing defined concentrations of of glucose (Means ± SD, n = 6). (B) Comparison of glucose (μg) detected in plasma versus levels detected from MN arrays inserted in the forearm of human volunteers at defined time points preceding (-1-0 h) and following (0–1, 1–2, 2–3 and 0–3 h) oral administration of 75 g of glucose (Means ± SD, n = 9).