Therapeutic Drug Monitoring of Vancomycin in Dermal Interstitial Fluid Using Dissolving Microneedles

Abstract

Objective: To design an alternative painless method for vancomycin (VCM) monitoring by withdrawing interstitial fluid (ISF) the skin using dissolving microneedles (DMNs) and possibly replace the conventional clinical blood sampling method.Methods: Male Wistar rats were anesthetized with 50 mg/kg sodium pentobarbital. Vancomycin at 5 mg/mL in saline was intravenously administered via the jugular vein. ISF was collected from a formed pore at 15, 30, 45, 60, 75, 90, and 120 min after the DMNs was removed from the skin. In addition, 0.3 mL blood samples were collected from the left femoral vein.Results: The correlation between the plasma and ISF VCM concentrations was significantly strong (r = 0.676, p < 0.05). Microscopic observation of the skin after application of the DMNs demonstrated their safety as a device for sampling ISF.Conclusion: A novel monitoring method for VCM was developed to painlessly determine concentrations in the ISF as opposed to blood sampling.

Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid

“…After being centrifuged at 12 000 rpm for 10 min, the solution in the tube was transferred for molecule quantification. The glucose concentration in the hydrogel was tested using a Glucose Assay Kit (Sigma) and the vancomycin concentration in hydrogel was tested using the liquid chromatography‐mass spectrometry (LC‐MS)/MS system (API 4000) according to related work 59. The mobile phase was distilled water–methanol (9:1, v/v) at a flow rate of 0.2 mL min −1 .…”

Transport of Azithromycin into Extravascular Space in Rats

“…To investigate the distribution of AZM in ISF, we directly collected ISF samples from abdominal skin of rats by using a DMN array chip according to previously reported methods (16). Briefly, after intravenous administration of an AZM solution (10 mg/ml in 10% DMSO) to rats at a dose of 10 mg/kg, a DMN array chip was applied to hairless abdominal skin by using an applicator.…”

“…In a previous study, we successfully collected ISF samples directly from rat skin using dissolving microneedles (DMNs) (16). After a DMN array is stamped onto the skin, ISF can be obtained by applying negative pressure.…”

“…After a DMN array is stamped onto the skin, ISF can be obtained by applying negative pressure. Moreover, we successfully determined blood glucose levels and drug concentrations in ISF (16,17). To further ascertain the transport of AZM into the extravascular space, the present study was designed to measure total AZM concentrations in ISF of the skin of rats after intravenous administration of AZM by using DMNs.…”

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

“…Recently, this technique of ISF withdrawal has been proposed by Ito et al as a method of therapeutic drug monitoring, using the same chondroitin sulfate MNs previously studied for glucose measurement. The authors administered the antibiotic vancomycin to rats, pierced their skin using the polymeric MN arrays, and manually extracted dermal ISF with a pipette, allowing drug quantification by LC‐MS . While this study suffers the same drawbacks ordinarily associated with solid MNs, it further supports the potential to use MNs for quantifying a wider variety of analytes in the skin.…”