636. Shell-sheddable dendritic polyglycerol sulfates loaded with sunitinib for inhibition of tumor angiogenesis
H. Koeppe, D. Horn, J. Scholz, E. Quaas, S. Schötz, F. Reisbeck, K. Achazi, E. Mohammadifar, J. Dernedde, R. Haag – 2023
Induced angiogenesis, a specific hallmark of cancer, plays a vital role in tumor progression and can be targeted by inhibitors like sunitinib. Sunitinib is a small hydrophobic molecule suffering from low bioavailability and a short half-life in the bloodstream. To overcome these drawbacks, suitable drug delivery systems need to be developed. In this work dendritic polyglycerol (dPG), a well-known polymer, was functionalized with a sheddable shell. Therefore, aliphatic chains of different lengths (C5, C9, C11) were coupled to dPG through a cleavable ester bond. To restore water solubility and improve tumor targeting, the surface was decorated with sulfate groups. The resulting shell-sheddable dPG sulfates were characterized and evaluated regarding their loading capacity and biocompatibility in cell culture. The nine-carbon chain derivative (dPG-TNS) was selected as the best candidate for further experiments due to its high drug loading capacity (20 wt%), and a sustained release in vitro. The cellular biocompatibility of the blank carrier up to 1 mg/mL was confirmed after 24 h incubation on HeLa cells. Furthermore, the shell-cleavability of dPG-TNS under different physiological conditions was shown in a degradation study over four weeks. The activity of sunitinib-loaded dPG-TNS was demonstrated in a tube formation assay on Human umbilical vein endothelial cells (HUVECs). Our results suggest that the drug-loaded nanocarrier is a promising candidate to be further investigated in tumor treatments, as it shows similar efficacy to free sunitinib while overcoming its limitations.