Cytocompatible Hyperbranched Polyesters Capable of Altering the Ca²⁺ Signaling in Neuronal Cells In Vitro

Synthetic hyperbranched polyesters with potential therapeutic properties were synthesized using the bifunctional polyethylene glycol or PEG with different molecular weights, ca., 4000, 6000, and 20,000 g/mol, and the trifunctional trans-aconitic acid or TAA. During polycondensation, a fixed amount of PEG was allowed to react with varying amounts of TAA (1:1 and 1:3) to control the branching extents. It was found that the synthetic polyesters had a considerable yield and were highly water soluble. Spectroscopic data (Fourier transform infrared and ¹H NMR) confirmed the polyester formation; the branching percentages were determined from ¹H NMR spectroscopy which varied from 73% to 22% among the synthesized samples. As the molecular weight of PEG was increased, the branching percentage drastically dropped. All polyesters were found to be negatively charged due to the ionization of unreacted -COOH in the branched ends at the working pH (7.4). Both the hydrodynamic size and intrinsic viscosity were found to reduce as the branching extent increased. Among the sets of polyesters, the one with the highest branching percentage (73%) showed the core-shell morphology (evident from field emission scanning electron microscopy and transmission electron microscopy studies). It also exhibited the highest efficiency toward Ca²⁺ influx in neuronal cells due to the unique morphology and the negatively charged surface. Nevertheless, this particular grade of polyester along with all the other grades was cytocompatible and induced reactive oxygen species generation. Since the maximally branched grade was highly efficient in altering the Ca²⁺ signaling through stronger influx, it may well be tested for treating neuronal disorders in vivo in future.