Long-term calibration considerations during subcutaneous microdialysis sampling in mobile rats

Abstract

The level at which implanted sensors and sampling devices maintain their calibration is an important research area. In this work, microdialysis probes with identical geometry and different membranes, polycarbonate/polyether (PC) or polyethersulfone (PES), were used with internal standards (vitamin B12 (MW 1355), antipyrine (MW 188) and 2-deoxyglucose (2-DG, MW 164)) and endogenous glucose to investigate changes in their long-term calibration after implantation into the subcutaneous space of Sprague-Dawley rats. Histological analysis confirmed an inflammatory response to the microdialysis probes and the presence of a collagen capsule. The membrane extraction efficiency (percentage delivered to the tissue space) for antipyrine and 2-DG was not altered throughout the implant lifetime for either PC- or PES-membranes. Yet, Vitamin B12 extraction efficiency and collected glucose concentrations decreased during the implant lifetime. Antipyrine was administered i.v. and its concentrations obtained in both PC-and PES-membrane probes were significantly reduced between the implant day and seven (PC) or 10 (PES) days post implantation suggesting that solute supply is critical for in vivo extraction efficiency. For the low molecular weight solutes such as antipyrine and glucose, localized delivery is not affected by the foreign body reaction, but recovery is significantly reduced. For Vitamin B12, a larger solute, the fibrotic capsule formed around the probe significantly restricts diffusion from the implanted microdialysis probes.

Effects of delayed delivery of dexamethasone-21-phosphate via subcutaneous microdialysis implants on macrophage activation in rats

“…These studies have shown that tissue surrounding dexamethasone eluting materials are characterized as having reduced cellular density. We have previously reported that immediate infusion of Dex results in a loose capsule surrounding the dialysis probe resulting in difficulties in obtaining the tissue for histological analysis[37, 71]. However, with delayed Dex infusion, the results demonstrated an increased cellular density surrounding the treatment probe as compared to the control probe.…”

Separation-Based Methods Combined With Microdialysis Sampling for Monitoring Neurotransmitters and Drug Delivery to the Brain

“…They have shown that continuous calibrations must be performed during longterm (ten day) in vivo peripheral microdialysis sampling experiments, as there is a decrease in recovery that is due to the progression of the foreign body response over time, regardless of analyte size (Mou et al, 2010). Additionally, it was found that large molecules (such as vitamin B12) exhibited a decrease in deliv ery over time, while smallersized molecules (antipyrine and 2deoxyglucose) showed no change in delivery into tissue when retrodialysis was performed in these longterm experiments (Mou et al, 2010).…”

Microdialysis sampling techniques applied to studies of the foreign body reaction

“…In the case of subcutaneous work, two microdialysis probes can be implanted in the same animal, one serving as the control and the other used to deliver bioactive chemicals. If bioactive agents are not desired to pass through the probe, other compounds that serve to monitor different aspects of the tissue biochemistry, such as 2-deoxyglucose, can be included in the perfusion fluid (Mou et al, 2010). …”

“…Using the dual delivery/sample collection microdialysis technique, our laboratory has employed various strategies to advance the delivery and recovery of cytokines and other signaling molecules to better evaluate the FBR (Ao et al, 2004; Ao and Stenken, 2006; Duo and Stenken, 2011a; Duo and Stenken, 2011b; Mou et al, 2010; Wang and Stenken, 2009a). Modulation of the FBR is not only significant in biomaterials science, but moderating the effects of the FBR specifically upon implantation of a microdialysis sampling device will also be crucial to furthering drug development for a variety of fields in pharmaceutical and clinical research.…”