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

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 at the tissue-sensor interface. Porous polyurethane coatings were produced by the salt-leaching/gas-foaming method. Scanning electron microscopy and micro-computed tomography (micro-CT) showed controlled porosity and coating thickness. In vitro drug release from coatings monitored over 2 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.

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

© 2014 Acta Materialia Inc.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 at the tissue-sensor interface. Porous polyurethane coatings were produced by the salt-leaching/gas-foaming method. Scanning electron microscopy and micro-computed tomography (micro-CT) showed controlled porosity and coating thickness. In vitro drug release from coatings monitored over 2 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.

Improving Indwelling Glucose Sensor Performance: Porous, Dexamethasone-Releasing Coatings that Modulate the Foreign Body Response

Inflammation and the formation of an avascular fibrous capsule have been identified as the key factors controlling the wound healing associated failure of implantable glucose sensors. Our aim is to guide advantageous tissue remodeling around implanted sensor leads by the temporal release of dexamethasone (Dex), a potent anti-inflammatory agent, in combination with the presentation of a stable textured surface.

First, Dex-releasing polyurethane porous coatings of controlled pore size and thickness were fabricated using salt-leaching/gas-foaming technique. Porosity, pore size, thickness, drug release kinetics, drug loading amount, and drug bioactivity were evaluated. In vitro sensor functionality test were performed to determine if Dex-releasing porous coatings interfered with sensor performance (increased signal attenuation and/or response times) compared to bare sensors. 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.

The tissue modifying effects of Dex-releasing porous coatings were accessed by fully implanting Tygon® tubing in the subcutaneous space of healthy and diabetic rats. Based on encouraging results from these studies, we deployed Dex-releasing porous coatings from the tips of functional sensors in both diabetic and healthy rats. We evaluated if the tissue modifying effects translated into accurate, maintainable and reliable sensor signals in the long-term. Sensor functionality was accessed by continuously monitoring glucose levels and performing acute glucose challenges at specified time points.

Sensors treated with porous Dex-releasing coatings showed diminished inflammation and enhanced vascularization of the tissue surrounding the implants in healthy rats. Functional sensors with Dex-releasing porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicated that Dex-loaded porous coatings were able to elicit a favorable tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo.

The diabetic pilot animal study showed differences in wound healing patters between healthy and diabetic subjects. Diabetic rats showed lower levels of inflammation and vascularization of the tissue surrounding implants when compared to their healthy counterparts. Also, functional sensors treated with Dex-releasing porous coatings did not show enhanced sensor sensitivity over a 21-day period. Moreover, increased in sensor signal lag and MARD scores were present in porous coated sensors regardless of Dex-loading when compared to bare implants. These results suggest that the altered wound healing patterns presented in diabetic tissues may lead to premature sensor failure when compared to sensors implanted in healthy rats.

Coupled 3-D finite difference time domain and finite volume methods for solving microwave heating in porous media

Computational results for the microwave heating of a porous material are presented in this paper. Combined finite difference time domain and finite volume methods were used to solve equations that describe the electromagnetic field and heat and mass transfer in porous media. The coupling between the two schemes is through a change in dielectric properties which were assumed to be dependent both on temperature and moisture content. The model was able to reflect the evolution of temperature and moisture fields as the moisture in the porous medium evaporates. Moisture movement results from internal pressure gradients produced by the internal heating and phase change.

Heat and mass transfer in two-phase porous materials under intensive microwave heating

Computational results for the intensive microwave heating of porous materials are presented in this work. A multi-phase porous media model has been developed to predict the heating mechanism. Combined finite difference time-domain and finite volume methods were used to solve equations that describe the electromagnetic field and heat and mass transfer in porous media. The coupling between the two schemes is through a change in dielectric properties which were assumed to be dependent both on temperature and moisture content. The model was able to reflect the evolution of both temperature and moisture fields as well as energy penetration as the moisture in the porous medium evaporates. Moisture movement results from internal pressure gradients produced by the internal heating and phase change.

A new computational approach to microwave heating of two-phase porous materials

Computational results for the microwave heating of a porous material are presented in this paper. Combined finite difference time domain and finite volume methods were used to solve equations that describe the electromagnetic field and heat and mass transfer in porous media. The coupling between the two schemes is through a change in dielectric properties which were assumed to be dependent on both temperature and moisture content. The model was able to reflect the evolution of both temperature and moisture fields as well as energy penetration as the moisture in the porous medium evaporates. Moisture movement results from internal pressure gradients produced by the internal heating and phase change.

Can Pickering emulsion formation aid the removal of creosote DNAPL from porous media?

The purpose of this investigation was to examine the proposition that creosote, emplaced in an initially water saturated porous system, can be removed from the system through Pickering emulsion formation. Pickering emulsions are dispersions of two immiscible fluids in which coalescence of the dispersed phase droplets is hindered by the presence of colloidal particles adsorbed at the interface between the two immiscible fluid phases. Particle trapping is strongly favoured when the wetting properties of the particles are intermediate between strong water wetting and strong oil wetting. In this investigation the necessary chemical conditions for the formation of physically stable creosote-in-water emulsions protected against coalescence by bentonite particles were examined. It was established that physically stable emulsions could be formed through the judicious addition of small amounts of sodium chloride and the surfactant cetyl-trimethylammonium bromide. The stability of the emulsions was initially established by visual inspection. However, experimental determinations of emulsion stability were also undertaken by use of oscillatory rheology. Measurements of the elastic and viscous responses to shear indicated that physically stable emulsions were obtained when the viscoelastic systems showed a predominantly elastic response to shearing. Once the conditions were established for the formation of physically stable emulsions a "proof-of-concept" chromatographic experiment was carried out which showed that creosote could be successfully removed from a saturated model porous system. (C) 2007 Elsevier Ltd. All rights reserved.

Textural and structural properties of bioactive glasses in the system CaO-SiO2

Gel-derived CaO-SiO2 binary glasses of CaO mole fractions 0. 2, 0.3 and 0. 4 have been prepared and characterised. Pore diameter specific pore volume, skeletal density and porosity were found to increase with increasing CaO-content, whereas a concomitant decrease in specific surface area was observed. Si-29 NMR indicated that the 0.2 CaO mole fraction glass consisted of higly polymerized Q(4) and Q(3) silicate species, with some Q(2) units. With increasing CaO mole fraction, these silicate species became progressively depolymerised such that isolated SiO4 tetrahedra were detected within the 0.4 CaO glass matrix. Unusually, the glasses retained a proportion of Q(4) and Q(3) species as the CaO mole fraction was increased. All glass formulations exhibited in vitro bioactivity. The rate of hydroxyapatite precipitation followed the order 0.2 CaO > 0.4 CaO > > 0.3 CaO, an effect that is attributed to differences in the rate of dissolution of calcium from these glasses. This, in turn, appears to be dependent upon the proportion of Ca 21 participating in the formation of the glassy network.

A metal-organic gel used as a template for a porous organic polymer

A polymeric metal-organic gel is described, which acts as a template in the preparation of macroporous polymethylmethacrylate, and can be easily removed post polymerisation.

Polymer nanotubes by wetting of ordered porous templates

We have developed a simple technique for the fabrication of polymer nanotubes with a monodisperse size distribution and uniform orientation. When either a polymer melt or solution is placed on a substrate with high surface energy, it will spread to form a thin film, known as a precursor film, similar to the behavior of low molar mass liquids. Similar wetting phenomena occur if porous templates are brought into contact with polymer solutions or melts: A thin surface film will cover the pore walls in the initial stages of wetting. This is because the cohesive driving forces for complete filling are much weaker than the adhesive forces. Wall wetting and complete filling of the pores thus take place on different time scales. The latter is prevented by thermal quenching in the case of melts or by solvent evaporation in the case of solutions, thus preserving a nanotube structure. If the template is of monodisperse size distribution, aligned or ordered, so are the nanotubes, and ordered polymer nanotube arrays can be obtained if the template is removed. Any melt-processible polymer, such as polytetrafluoroethylene (PTFE), blends, or multicomponent solutions can be formed into nanotubes with a wall thickness of a few tens of nanometers. Owing to its versatility, this approach should be a promising route toward functionalized polymer nanotubes.