Inappropriate pharmacokinetic has been recognized as being one of the major factors leading to the withdrawal of new chemical entities from drug development. Therefore, a large number of compounds has to be screened before matching one drug candidate disclosing good ADMET properties during the early stage of drug discovery. In vitro high throughput methods thus become tools of choice to assess compounds pharmacokinetics and in particular their ability to penetrate biological membranes such as the blood-brain barrier (BBB). This thesis aimed to develop a new in vitro high throughput artificial membrane able to predict passive transendothelial permeability of drug small molecules through the BBB with PAMPA. This new method was then applied to more complex matrices, such as the natural products and the nanotransporters, in order to understand their mode of permeation through the BBB and assess their impact on the central nervous system.