The major aim of this study was to better understand the importance of autocatalysis in poly(lactic-co-glycolic acid) (PLGA)-based microparticles used as controlled drug delivery systems. Upon contact with biological fluids, PLGA is degraded into shorter chain alcohols and acids. An accumulation of the latter can lead to significant drops in micro-pH and subsequent accelerated polymer degradation. The system size, determining the diffusion path lengths, plays a crucial role for the occurrence/absence of autocatalytic effects. Using an oil-in-water solvent-extraction/evaporation process, different-sized drug-free and drug-loaded, PLGA-based microparticles were prepared and physicochemically characterized (SEM, DSC, SEC, optical microscopy, and UV-spectrophotometry) before and upon exposure to simulated biological fluids. Based on these experimental results, an adequate mathematical theory was developed describing the dominating mass transfer processes and chemical reactions. Importantly, a quantitative relationship could be established between the dimension of the device and the resulting drug release patterns, taking the effects of autocatalysis into account.

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In a series of experiments, we investigated the dependence of contextual cueing on working memory resources. A visual search task with 50 % repeated displays was run in order to elicit the implicit learning of contextual cues. The search task was combined with a concurrent visual working memory task either during an initial learning phase or a later test phase. The visual working memory load was either spatial or nonspatial. Articulatory suppression was used to prevent verbalization. We found that nonspatial working memory load had no effect, independent of presentation in the learning or test phase. In contrast, visuospatial load diminished search facilitation in the test phase, but not during learning. We concluded that visuospatial working memory resources are needed for the expression of previously learned spatial contexts, whereas the learning of contextual cues does not depend on visuospatial working memory.