Biorasis (United States)

An anti-inflammatory drug-loaded composite coating (dexamethasone-loaded poly (lactic-co-glycolic acid) [PLGA] microspheres/polyvinyl alcohol [PVA] hydrogel) was previously developed to counter the foreign body reaction to a fully implantable continuous glucose monitoring biosensor. The long-term sensor functionality was ensured in the presence of the drug-loaded composite coating thus facilitating better diabetes control and management. In order to advance such a drug-device combination product toward clinical testing, addressing sterilization remains a key step due to the heterogeneity of the product components. The main objective of this research was to investigate the effect of two terminal sterilization techniques: gamma radiation and ethylene oxide (EO) on the stability of the anti-inflammatory coatings as well as retention of the glucose sensing ability of the implantable sensor. The composite coatings, their individual components, and the glucose-sensing elements of the biosensor were subjected to low-temperature gamma radiation and EO cycles. Detailed characterization was conducted on all components before and after sterilization. Exposure to gamma radiation affected dexamethasone crystallinity and glucose response linearity of the sensing element, whereas physical aging of microspheres in composite coatings was observed poststerilization with EO. Despite these effects, dexamethasone drug release from coatings was not significantly affected by either technique. The research findings indicate that both sterilization techniques are feasible for the sterilization of the dexamethasone-loaded PLGA microspheres/PVA hydrogel composite coatings, while EO was preferred for the sterilization of the glucose-sensing element of the biosensor.

The design and fabrication of multi-layer amperometric electrochemical glucose sensors is dependent upon the diffusional kinetics of the chemical/biochemical species which contribute to the sensor’s response. Considerable effort has been carried out to coat the working electrode with appropriate glucose flux-limiting membranes which is pertinent for superior in vivo performance, and hence requires a careful understanding of the participating species within the sensor cross-sectional architecture. This contribution reports the computational modeling of Clark’s first generation amperometric glucose sensor coated with an electro-polymerized glucose oxidase (GOx) layer along with a layer of polyurethane (PU) employed to reduce the glucose-influx in order to generate linear operation over the normal physiological glucose range in vivo. The model was programmed using MATLAB and utilizes the finite-difference method for the solution to the enzymatic reaction-based diffusion equations. Additionally, experimental devices were fabricated, tested and compared with the simulated results. The simulation of these devices have been shown to align well with experimentally fabricated devices in terms of amperometric current density. The increase in device linearity with the addition of the outer glucose-flux limiting PU membrane corroborate our experimental findings reported in this study which can be used as a powerful analytical tool in designing high–performance next generation implantable glucose sensors.

The function of implantable glucose sensor is hindered by post-implantation effects such as biofouling and negative tissue responses both of which lead to permeability reducing fibrous encapsulation. Utilization of drug-eluting composite coatings based on dexamethasone-containing poly (lactic-co-glycolic) acid (PLGA) microspheres and poly (vinyl alcohol) (PVA) hydrogel matrix has been shown to suppress inflammation over a period of 1–3 months. Herein, it is shown that these coatings provide another auxiliary venue to offset the negative effects of protein adsorption through generation of macroscopic porosity following microsphere degradation. Long-term studies in serum have indicated that, while biofouling clogs the microporosity of the hydrogel, it has been offset by the generated macroscopic porosity following microsphere degradation. This resulted in a two-fold recovery in sensor sensitivity as compared to controls. These findings suggest that the use of macroscopic porosity can reduce biofouling-induced sensitivity losses, an approach synergistic with drug-delivery based methodologies to mitigate negative tissue responses.