Hydrogel-Coated\nSERS Microneedles for Drug Monitoring\nin Dermal Interstitial Fluid

Abstract

<i>In vivo</i> drug monitoring is crucial for\nevaluating\nthe effectiveness and safety of drug treatment. Blood sampling and\nanalysis is the current gold standard but needs professional skills\nand cannot meet the requirements of point-of-care testing. Dermal\ninterstitial fluid (ISF) showed great potential to replace blood for <i>in vivo</i> drug monitoring; however, the detection was challenging,\nand the drug distribution behavior in ISF was still unclear until\nnow. In this study, we proposed surface-enhanced Raman spectroscopy\n(SERS) microneedles (MNs) for the painless and real-time analysis\nof drugs in ISF after intravenous injection. Using methylene blue\n(MB) and mitoxantrone (MTO) as model drugs, the innovative core–satellite\nstructured Au@Ag SERS substrate, hydrogel coating over the MNs, rendered\nsensitive and quantitative drug detection in ISF of mice within 10\nmin. Based on this technique, the pharmacokinetics of the two drugs\nin ISF was investigated and compared with those in blood, where the\ndrugs were analyzed via liquid chromatography–mass spectrometry.\nIt was found that the MB concentration in ISF and blood was comparable,\nwhereas the concentration of MTO in ISF was 2–3 orders of magnitude\nlower than in blood. This work proposed an efficient tool for ISF\ndrug monitoring. More importantly, it experimentally proved that the\npenetration ratio of blood to ISF was drug-dependent, providing insightful\ninformation into the potential of ISF as a blood alternative for <i>in vivo</i> drug detection.