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Heparin-gold nanoparticles for enhanced microdialysis sampling.

ABSTRACT: Cerebral microdialysis is a sampling technique which offers much potential for understanding inflammatory pathophysiology following traumatic brain injury (TBI). At present, the recovery of cytokines via microdialysis in clinical studies is not straightforward primarily due to their size, steric properties and low concentrations. Heparin and heparin-coated microspheres have previously shown promise as cytokine-binding agents for enhanced microdialysis sampling in animal models (Duo and Stenken in Anal Bioanal Chem 399(2):773-82, 2011; Anal Bioanal Chem 399(2):783-93, 2011). However, there are several factors limiting application for microdialysis in patients. The aim of this study was to produce heparin-coated gold nanoparticles as cytokine capture agents for enhanced microdialysis sampling, potentially applicable to a clinical setting. Gold nanoparticles (AuNP) were chemically conjugated to heparin via a bifunctional polyethylene glycol (PEG) linker. The heparin-AuNP (AuNP-Hep) were characterised, demonstrating the successful addition of heparin to the gold surface. The performance of the AuNP-Hep during in vitro testing was compared both to current methodology (Helmy et al. in J Neurotrauma 26(4):549-61, 2009) and to the heparin-coated microspheres developed by Duo and Stenken (Anal Bioanal Chem 399(2):773-82, 2011; Anal Bioanal Chem 399(2):783-93, 2011). The AuNP-Hep yielded a higher recovery of cytokines compared to current methodology and heparin-coated microspheres, during in vitro testing designed to mimic the human environment and the intensive care unit. In this study, AuNP-Hep were developed for enhanced microdialysis sampling of cytokines, potentially applicable in a clinical setting. Based on the success of the AuNP-Hep in vitro, the proposed method offers an alternative to the use of current protocols that rely on a blood product (albumin) for microdialysis sampling of cytokines in patients.

SUBMITTER: Giorgi-Coll S

PROVIDER: S-EPMC5534206 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Heparin-gold nanoparticles for enhanced microdialysis sampling.

Giorgi-Coll Susan S Blunt-Foley Holly H Hutchinson Peter J PJ Carpenter Keri L H KLH

Analytical and bioanalytical chemistry 20170629 21

Cerebral microdialysis is a sampling technique which offers much potential for understanding inflammatory pathophysiology following traumatic brain injury (TBI). At present, the recovery of cytokines via microdialysis in clinical studies is not straightforward primarily due to their size, steric properties and low concentrations. Heparin and heparin-coated microspheres have previously shown promise as cytokine-binding agents for enhanced microdialysis sampling in animal models (Duo and Stenken i ...[more]

PMID: 28664332

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Project description:Sampling the concentration of insulin in human skin using microdialysis is challenging because of low intracutaneous concentrations and low recovery, presumably due to adsorption of insulin to the microdialysis system. In this study, we aimed to (1) measure how the concentration of insulin varies in three different tissue compartments (intracutaneous, subcutaneous and intravenous) and (2) to study how much insulin is adsorbed to the microdialysis catheter membranes and tubing during a typical microdialysis experiment, both in vivo and in vitro. We hypothesized that (1) the concentration of insulin decreases from the intravenous compartment to the intracutaneous and subcutaneous tissue, and that (2) adsorption of insulin to the microdialysis membrane and tubing impairs the recovery of insulin from the tissue. In this experimental study, microdialysis catheters were inserted intracutaneously, subcutaneously and intravenously in 11 healthy subjects. Systemic endogenous hyperinsulinemia was induced by intake of an oral glucose load. Insulin concentration was measured in the dialysate and in the extracted samples from the catheter membrane and tubings. In vitro microdialysis was performed to investigate the temporal resolution of the adsorption. After an oral glucose load insulin concentration increased intravenously, but not in the intracutaneous or subcutaneous compartments, while glucose, lactate and pyruvate concentrations increased in all compartments. The adsorption of insulin to the microdialysis membrane in vivo was highest in the intravenous compartment (p = 0.01), compared to the intracutaneous and subcutaneous compartments. In vitro, the adsorption to the microdialysis membrane was highest one hour after sampling, then the concentration gradually decreased after three and five hours of sampling. The concentration of insulin in peripheral tissues is low, probably due to decreasing tissue vascularity. Adsorption of insulin to the microdialysis membrane is modest but time-dependent. This finding highlights the importance of a stabilization time for the microdialysis system before sampling tissue analytes.

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Heparin-gold nanoparticles for enhanced microdialysis sampling.

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Heparin-gold nanoparticles for enhanced microdialysis sampling.

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