Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid.
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ABSTRACT:
SUBMITTER: Zhu J
PROVIDER: S-EPMC7182487 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Interstitial fluid (ISF) is a body fluid that fills, surrounds cells and contains various biomarkers, but it has been challenging to extract ISF in a reliable and sufficient amount with high speed. To address the issues, we developed the tilted microneedle ISF collecting system (TMICS) fabricated by 3D printing. In this system, the microneedle (MN) was inserted at 66° to the skin by TMICS so that the MN length could be extended within a safe range of skin penetration. Moreover, TMICS incorporating three MN patches created reliable ISF collecting conditions by penetrating the skin at consistent angle and force, 4.9 N. Due to the MN length increase and the patch number expansion, the surface area of the penetrated tissue was increased, thereby confirming that ISF extraction efficiency was improved. Skin ISF was collected into the paper reservoir on the patch, and the absorbed area was converted into a volume. ISF extraction from the rat skin in vivo by TMICS was well tolerated, and the 2.9 μL of ISF was obtained within 30 s. Therefore, TMICS is promising to apply in the diagnosis of multiple biomarkers in ISF with high speed and stability.
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Project description:Tissue interstitial fluid (ISF) surrounds cells and is an underutilized source of biomarkers that complements conventional sources such as blood and urine. However, ISF has received limited attention due largely to lack of simple collection methods. Here, we developed a minimally invasive, microneedle-based method to sample ISF from human skin that was well tolerated by participants. Using a microneedle patch to create an array of micropores in skin coupled with mild suction, we sampled ISF from 21 human participants and identified clinically relevant and sometimes distinct biomarkers in ISF when compared to companion plasma samples based on mass spectrometry analysis. Many biomarkers used in research and current clinical practice were common to ISF and plasma. Because ISF does not clot, these biomarkers could be continuously monitored in ISF similar to current continuous glucose monitors but without requiring an indwelling subcutaneous sensor. Biomarkers distinct to ISF included molecules associated with systemic and dermatological physiology, as well as exogenous compounds from environmental exposures. We also determined that pharmacokinetics of caffeine in healthy adults and pharmacodynamics of glucose in children and young adults with diabetes were similar in ISF and plasma. Overall, these studies provide a minimally invasive method to sample dermal ISF using microneedles and demonstrate human ISF as a source of biomarkers that may enable research and translation for future clinical applications.
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Project description:Glutathione is a natural anti-aging substance that prevents the oxidation of protein thiols from reactive oxygen species. In the pharmaceutical industry, reduced glutathione (GSH) has been widely used for skin whitening due to its ability to inhibit tyrosinase. However, its poor permeability and foul odor limit its use in skin applications. Herein, we report a GSH-loaded dissolving microneedle (MN) patch prepared with hyaluronic acid (HA) that enables enhanced permeation across the skin and reduces the foul odor of GSH. HA was selected to prepare odorless GSH solutions and used for MN fabrications as a carrier of GSH. GSH-loaded MN (GSH-MN) arrays prepared from MN-forming solution containing up to 10% GSH showed good pattern uniformity and appropriate mechanical properties for insertion into the skin. The GSH-MNs with a loading capacity of 17.4% dissolve within 10 min following insertion into porcine skin and release the loaded GSH without being oxidized. This new approach combines functional biopolymers to reduce the characteristic GSH odor and advanced transdermal delivery based on MN technology to enhance skin permeation without pain. We believe this technique could expand the application of GSH in many cosmeceutical fields.
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Project description:Individuals with diabetes can benefit considerably from continuous blood glucose monitoring. To address this challenge, a proof-of-concept was performed for continuous glucose monitoring (CGM) based on an enzymeless porous nanomaterial (pNM)-modified microneedle electrode array (MNEA). The pNM sensing layer was electrochemically deposited on MNs by applying a fixed negative current of -2.5 mA cm-2 for 400 s. The pNM-modified MNEA was packed using a biocompatible Nafion ionomer. The fabricated MNEAs were 600 × 100 × 150 µm in height, width, and thickness, respectively. The surfaces of the modified MNs were characterized by scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The fabricated MNEAs showed a wide dynamic range (1-30 mM) in phosphate-buffered saline (PBS) and in artificial interstitial fluid (ISF), with good sensitivities (PBS: 1.792 ± 0.25 µA mM-1 cm-2, ISF: 0.957 ± 0.14 µA mM-1 cm-2) and low detection limits (PBS: 7.2 µM, ISF: 22 µM). The sensor also showed high stability (loss of 3.5% at the end of 16 days), selectivity, and reproducibility (Relative standard deviations (RSD) of 1.64% and 0.70% for intra- and inter-assay, respectively) and a good response time (2 s) with great glucose recovery rates in ISF (98.7-102%).
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