NeuralCipher Research overview
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The blood-brain barrier (BBB) is composed of brain endothelial cells, pericytes, and astrocytes, which build a tight cellular barrier. Therapeutic (macro)molecules are not able to transit through the BBB in their free form. This limitation is bypassed by apolipoprotein E (ApoE)-functionalized polymeric nanoparticles (NPs) that are able to transport drugs (e.g. dalargin, loperamide, doxorubicin, nerve growth factor) across the BBB via low density lipoprotein (LDL) receptor mediated transcytosis. Coating with polysorbate 80 or poloxamer 188 facilitates ApoE adsorption onto polymeric NPs enabling recognition by LDL receptors of brain endothelial cells. This effect is even enhanced when NPs are directly coated with ApoE without surfactant anchor. Similarly, covalent coupling of ApoE to NPs that bear reactive groups on their surface leads to significantly improved brain uptake while avoiding the use of surfactants. Several in vitro BBB models using brain endothelial cells or co-cultures with astrocytes/pericytes/glioma cells are described which provide first insights regarding the ability of a drug delivery system to cross this barrier. In vivo models are employed to simulate central nervous system-relevant diseases such as Alzheimer's or Parkinson's disease and cerebral cancer.
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