Mechanisms of burst release from pH-responsive polymeric microparticles.

Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release.

ERP correlates of shared control mechanisms involved in saccade preparation and in covert attention

We investigated whether attention shifts and eye movement preparation are mediated by shared control mechanisms, as claimed by the premotor theory of attention. ERPs were recorded in three tasks where directional cues presented at the beginning of each trial instructed participants to direct their attention to the cued side without eye movements (Covert task), to prepare an eye movement in the cued direction without attention shifts (Saccade task) or both (Combined task). A peripheral visual Go/Nogo stimulus that was presented 800 ms after cue onset signalled whether responses had to be executed or withheld. Lateralised ERP components triggered during the cue–target interval, which are assumed to reflect preparatory control mechanisms that mediate attentional orienting, were very similar across tasks. They were also present in the Saccade task, which was designed to discourage any concomitant covert attention shifts. These results support the hypothesis that saccade preparation and attentional orienting are implemented by common control structures. There were however systematic differences in the impact of eye movement programming and covert attention on ERPs triggered in response to visual stimuli at cued versus uncued locations. It is concluded that, although the preparatory processes underlying saccade programming and covert attentional orienting may be based on common mechanisms, they nevertheless differ in their spatially specific effects on visual information processing.