Characterization of porous, dexamethasone-releasing polyurethane coatings for glucose sensors

Abstract

Commercially available implantable needle-type glucose sensors for diabetes management are robust analytically but can be unreliable clinically primarily due to tissue-sensor interactions. Here, we present the physical, drug release, and bioactivity characterization of tubular, porous dexamethasone (Dex) releasing polyurethane coatings designed to attenuate local inflammation in the tissue-sensor interface. Porous polyurethane coatings were produced by the salt-leaching/gas-foaming method. Scanning electron microscopy (SEM) and Micro-computed tomography (Micro-CT) showed a controlled porosity and coating thickness. In vitro drug release from coatings monitored over two weeks presented an initial fast release followed by a slower release. Total release from coatings was highly dependent on initial drug loading amount. Functional in vitro testing of glucose sensors deployed with porous coatings against glucose standards demonstrated that highly porous coatings minimally affected signal strength and response rate. Bioactivity of the released drug was determined by monitoring Dex-mediated, dose-dependent apoptosis of human peripheral blood derived monocytes in culture. Acute animal studies were used to determine the appropriate Dex payload for the implanted porous coatings. Pilot short-term animal studies showed that Dex released from porous coatings implanted in rat subcutis attenuated the initial inflammatory response to sensor implantation. These results suggest that deploying sensors with the porous, Dex-releasing coatings is a promising strategy to improve glucose sensor performance.

Porous, Dexamethasone-loaded polyurethane coatings extend performance window of implantable glucose sensors in vivo

“…Dex is a potent glucocorticoid associated with diminished activation of immune cells and up-regulation of anti-inflammatory cytokines [21, 29, 30], yet localized delivery of Dex is often accompanied by decreased vascularity at the sensor-tissue interface [20, 21, 30–32]. It is also well established that surface texturing with feature sizes on the order of cellular dimensions can induce blood vessel formation around medical implants [11, 25, 33–35]. …”

“…Previously we reported on the in vitro testing physical characterization, and initial in vivo testing of the Dex-loaded porous polyurethane coatings [25]. These coatings fit snugly on the surface of Medtronic MiniMed SOF-SENSOR™ glucose sensors, were highly porous (~85 %), and had a controlled thickness (~ 81 μm) and pore size (~76 μm).…”

“…Tissue changes in the form of an attenuated inflammatory response can be attributed to the timed and bioactive released of Dex from the coating surface. It has been previously reported that Dex-loaded porous coatings have a daily release of ~ 30 μg/day of bioactive Dex during the first 7 days, and a release daily release of ~7 μg from days 7–14 [25]. This amounted to almost a full deployment of Dex within the first 14 days, which is also the window when the greatest anti-inflammatory action was observed in the tissue surrounding Dex-loaded coatings (Fig 2b and 3b).…”

“…As detailed elsewhere [25], porous coatings were fabricated by gas-foaming/salt-leaching technique. Briefly, a polyurethane solution of 6.5% w/w was prepared by dissolving Tecoflex® 93A pellets (Lubrizol, Technologies) in a solution of 75:25 chloroform to ethanol ratio.…”

“…Previously, we reported on the characterization of porous polyurethane coatings with a controllable microstructure, tunable drug loading and bioactive release of Dexamethasone (Dex) [25]. However, questions regarding the effects of coatings on the FBR and subsequent effects on glucose sensor function still remained.…”