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Polyelectrolyte-coated Nanocapsules Containing Cyclosporine A Protect Neuronal-like Cells Against Oxidative Stress-induced Cell Damage
M. Piotrowski, D. Jantas, M. Leśkiewicz, K. Szczepanowicz, P. Warszyński, W. Lasoń
Published 2018 · Chemistry
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Abstract Experimental data have demonstrated the neuroprotective potential of cyclosporine A (CsA), however, its clinical usage as neuroprotectant is limited due to poor blood-brain barrier permeability and potential peripheral and central toxicity. In order to overcome these limitations, the nanoparticulate CsA delivery technology has been recently proposed to improve CsA immunosuppressive potential, however, its neuroprotective action has not been sufficiently studied. Thus, in the present study two types of (bio)polyelectrolyte-coated nanocapsules containing CsA (AOT/PLL-CsA and AOT/PLL/PGA-CsA) were synthesized using a nanoemulsification technique and the layer-by-layer (LbL) saturation method. By using human neuroblastoma SH-SY5Y cells, we demonstrated that CsA alone at a concentration above 0.1 μM had a cell-damaging effect. CsA at lower concentrations (0.1–10 nM) was devoid of toxicity and reduced the hydrogen peroxide (H2O2)-induced cell damage, whereas its higher contents (0.5 and 1 μM) increased oxidative stress-induced cell death. Further studies showed that both forms of nanoencapsulated CsA were biocompatible and protected SH-SY5Y cells against the H2O2-induced damage in the range of concentrations 0.04–0.16 μM, therefore, the proposed nanoformulations for CsA delivery are suitable to reduce its cytotoxic effects and enhance the neuroprotective activity against oxidative stress.
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