Microcapsule internalization by cells in vitro caused by physical and biochemical stimuli
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There is a growing interest in micro sized vehicles with the function of storing, targeting and controlled releasing of substances during the past few decades. However, delivering the desired drugs inside micro containers to living cells is a particular challenging topic of material science. Microcapsules made of polyelectrolyte multilayers exhibit low- or non-toxicity, appropriate mechanical stability, variable degradation and can incorporate remotely addressable release mechanisms in responding to stimuli and external triggering, making them well suitable for targeted drug delivery to live cells. This study investigates interactions between microcapsules made of synthetic (i.e. PSS/PAH) or natural (i.e. DS/PArg) polyelectrolyte and cells, with particular focus on the effect of the glycocalyx layer on the intake of microcapsules by human umbilical vein endothelial cells (HUVECs). Neuraminidase cleaves N-acetyl neuraminic acid residues of glycoproteins and targets the sialic acid component of the glycocalyx on the cell membrane. Three-dimensional CLSM images reveal that microcapsules functionalized with neuraminidase can be internalized by endothelial cells, whereas ones without neuraminidase are blocked by the glycocalyx layer. Uptake of the microcapsules is most significant in the first 2 hours. Following their internalization by endothelial cells, biodegradable DS/PArg capsules rupture by day 5, however, there is no obvious change in the shape and integrity of PSS/PAH capsules within the period of observation. Results from the study support our hypothesis that the glycocalyx functions as an endothelium barrier to cross membrane movement of microcapsules. Neuraminidase-loaded microcapsules can enter endothelial cells by cleaving the glycocalyx in their close proximity with minimum disruption of the glycocalyx layer, therefore they have high potential to act as drug delivery carriers to pass through the endothelium barrier of blood vessels into the surrounding tissue.
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