Objective: During deep brain stimulation (DBS) the electrode-tissue interface forms a critical path between device and brain tissue. Although changes in the electrical double layer and glial scar can impact stimulation efficacy, the effects of chronic DBS on the electrode-tissue interface have not yet been established. Approach: In this study, we characterised the electrode-tissue interface surrounding chronically implanted DBS electrodes in rats and compared the impedance and histological properties at the electrode interface in animals that received daily stimulation and in those where no stimulation was applied, up to eight weeks post-surgery. A computational model was developed based on the experimental data, which allowed the dispersive electrical properties of the surrounding encapsulation tissue to be estimated. The model was then used to study the effect of stimulation-induced changes in the electrode-tissue interface on the electric field and neural activation during voltage- and current-controlled stimulation. Main results: Incorporating the observed changes in simulations in silico, we estimated the frequency-dependent dielectric properties of the electrical double layer and surrounding encapsulation tissue. Through simulations we show how stimulation-induced changes in the properties of the electrode-tissue interface influence the electric field and alter neural activation during voltage-controlled stimulation. A substantial increase in the number of stimulated collaterals, and their distance from the electrode, was observed during voltage-controlled stimulation with stimulated ETI properties. In vitro examination of stimulated electrodes confirmed that high frequency stimulation leads to desorption of proteins at the electrode interface, with a concomitant reduction in impedance. Significance: The demonstration of stimulation-induced changes in the electrode-tissue interface has important implications for future DBS systems including closed-loop systems where the applied stimulation may change over time. Understanding these changes is particularly important for systems incorporating simultaneous stimulation and sensing, which interact dynamically with brain networks.

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Irbesartan (IRB) is a BCS class II drug with poorly aqueous solubility and its absorption is dissolution rate limited. In the present study solubility and dissolution rate of IRB were improved by nanonization and using two poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) amphiphiles, namely Pluronic® F127 and Pluronic® F68, as nanosuspension stabilisers. In addition, the role of these surfactants in the solubilization of the drug was assessed. The nanocrystals were produced by two top-down techniques- high shear homogenisation and ultra-probe sonication. The nanocrystals were characterized for particle size, size distribution and zeta potential and compared to the unprocessed drug by FTIR, thermal analysis, scanning electron microscopy, solubility and dissolution rate. IRB nanocrystals showed greater solubility and faster dissolution rate than the original drug, solubility being higher for formulations prepared with F127 than those with F68. Presence of an endothermic peak of drug in the formulation confirmed its crystalline nature, regardless of the use of two energetic methods. SEM of the nanocrystals revealed a small rod-shaped morphology and the substantial decrease of the particles size. Overall results support these nanonization techniques as a simple, cost-effective and scalable approach to improve the aqueous solubility of drugs such as IRB that are classified into Class II of the Biopharmaceutic Classification System (BCS).