In Vitro Biocompatibility and Endothelial Permeability of Branched Polyglycidols Generated by Ring-Opening Polymerization of Glycidol with B(C 6 F 5 ) 3 under Dry and Wet Conditions.

Polyglycidol or polyglycerol (PG), a polyether widely used in biomedical applications, has not been extensively studied in its branched cyclic form ( bc PG), despite extensive research on hyperbranched PG (HPG). This study explores the biomedical promise of bc PG, particularly its ability to cross the blood-brain barrier (BBB). We evaluate in vitro biocompatibility, endothelial permeability, and formation of branched linear PG ( bl PG) as topological impurities in the presence of water. Small angle X-ray scattering in solution revealed a fractal dimension of approximately two for bc PG and the mixture bc+bl PG, suggesting random branching. Comparisons of cytotoxicity and endothelial permeability between bc PG, bc+bl PG, and HPG in a BBB model using hCMEC/D3 cells showed different biocompatibility profiles and higher endothelial permeability for HPG. bc PG showed a tendency to accumulate around cell nuclei, in contrast to the behavior of HPG. This study contributes to the understanding of the influence of polymer topology on biological behavior.