Prediction of blood-brain barrier permeability using modified poly(dimethylsiloxane)

Blood-brain barrier (BBB) permeability of drugs is fundamental to understand yet incredibly difficult to measure, or even, predict. This study proposes the adoption of a chemically modified form of poly(dimethylsiloxane) (PDMS) as an in vitro biomedical mimic of the BBB for pharmaceutical analysis. Initially, a series of untreated PDMS membrane thicknesses (0.02 to 0.4 mm) were studied to review the permeation of 15 model compounds to ultimately select the most suitable material for further modification. This was deemed to be 0.2 mm for maximising permeability range, maintaining experimental ease of use and also similarity to in vivo BBB thickness. Five distinct membranes were then created and subsequently analysed with the same 15 compounds to determine the most suitable BBB mimic through correlation with literature data. Ultimately, a strong correlation was found between published BBB values and cumulative permeation through the hydrophobic DPPC-coated form of PDMS (r² = 0.75) based on its similarity to the lipid-rich BBB environment. This then facilitated prediction of BBB values for compounds where no literature data has ever been listed. It is proposed that analysing permeation of novel pharmaceutical compounds using the DPPC-coated PDMS can help researchers predict BBB permeation using an in vitro technique thus facilitating prediction and helping understand drug behaviour in the body.