IMMUNOLIPOSOMES – A NEW THERAPEUTIC OPTION TO TREAT SYNGAP1-ASSOCIATED EPILEPSY

The blood-brain barrier (BBB) prevents the uptake of most drugs into the brain. Thus, active processes, physiologically necessary for nutrient uptake, like receptor-mediated transcytosis have become interesting targets for drug transport. One such receptor is the transferrin receptor 1 (TfR), which is highly expressed at the BBB. Immunoliposomes targeting the TfR were loaded with Rosuvastatin to improve the therapy of SynGAP1-associated epilepsy. The rationale of using Rosuvastatin is based on its function downregulating the Ras-Raf-MEK-ERK pathway, which is upregulated in excitatory neurons in SynGAP1 patients. However, Rosuvastatin shows poor BBB permeability. Therefore, immuno-liposomes decorated with an anti-TfR antibody were prepared and characterized. The liposomes could be prepared reproducibly with a size of about 125 nm, they were not hemolytically active and showed colloidal stability in plasma for 2 hours. They showed a high binding to bEnd.3 brain capillary endothelial cells which was not altered in presence of the natural ligand transferrin. After in vivo administration fluorescently labeled immunoliposomes exhibited a long plasma half-life of more than 2 hours and accumulation in brain capillaries. In comparison to unmodified liposomes, anti-TfR antibody coupled immunoliposomes showed a 2.8 improved transfer of Rosuvastatin into brain tissue, indicating successful passage across the BBB.
These liposomes represent a technology platform, which can be used for drug delviery across the BBB beyond SynGAP1 associated epilepsy