There are many diseases of the central nervous system (CNS), like Parkinson's disease, Alzheimer's disease, depression, schizophrenia, epilepsy, migraine headache, and HIV infection in the brain.... Show moreThere are many diseases of the central nervous system (CNS), like Parkinson's disease, Alzheimer's disease, depression, schizophrenia, epilepsy, migraine headache, and HIV infection in the brain. However, treatment is difficult since many drugs cannot reach the brain in sufficient quantities due to the existence of the blood-brain barrier (BBB). This barrier is situated at the interface of blood and brain and its primary function is to maintain the homeostasis of the brain. The research described in this thesis was initiated to meet the challenge of drug delivery across the BBB. The focus was to explore the possibilities for drug delivery to the brain via the transferrin receptor (TfR). Although drug delivery to the brain via the TfR is not selective, it is effective. A mechanistic approach was chosen in which the binding and association of Tf, Tf-drug conjugates and Tf-tagged liposomes by BCEC in vitro was determined. The efficiency of delivery depends mainly on the size of the cargo: a 40 kDa protein does not affect the association of Tf by the TfR, while a liposomal drug carrier (100 nm in diameter) affects both the association and the intracellular routing. Show less
