Evaluation of Biotinylated PAMAM Dendrimer Toxicity in Models of the Blood Brain Barrier: A Biophysical and Cellular Approach

Abstract

The interaction of biotinylated G4 poly(amidoamine) (PAMAM) dendrimer conjugates and G4 PAMAM dendrimers with in vitro models of the blood brain barrier (BBB) was evaluated using Langmuir Blodgett monolayer techniques, atomic force microscopy (AFM) and lactate dehydrogenase measures of cell membrane toxicity. Results indicate that both G4 and G4 biotinylated PAMAM dendrimers disrupt the composition of the liquid condensed (LC) and liquid expanded (LE) phases of the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayer. The disruption is concentration dependent and more marked for G4 biotinylated PAMAMs. Lactate dehydrogenase (LDH) assays using endothelial cell culture models of the BBB indicate that biotinylation results in higher levels of toxicity than non-biotinylation. This approach provides valuable information to assess nanoparticle toxicity for drug delivery to the brain.