Sulfated β-cyclodextrins (S-β-CDs) are useful excipients for improving the solubility of drugs. One such formulation incorporating 5-fluorouracil (5-FU), termed FD(S), showed improved efficacy over 5-FU alone in orthotopic carcinoma xenograft models [1]. S-β-CDs have heparin-like anti-coagulant and anti-angiogenic properties, which may have contributed to the improved anti-tumour effect of FD(S). While the anti-coagulant nature of S-β-CDs was established, the anti-angiogenic properties of S-β-CDs within FD(S) were still unconfirmed. In this study, we assess the effect of S-β-CD, alone and within FD(S), on the proliferation and migration of endothelial cells in live-cell kinetic assays, and the reorganisation of human umbilical vein endothelial cells into tubule structures in vitro. Confirmation of the anti-angiogenic effect of S-β-CD was demonstrated using an ex ovo chick embryo chorioallantoic membrane (CAM) assay. S-β-CD alone and within FD(S) significantly inhibited angiogenesis by impeding endothelial cell migration. This suggests that in addition to the cytotoxic action of the drug 5-FU, therapeutic inhibition of angiogenesis by S-β-CDs within FD(S) could potentially limit local invasion and metastases. This has important implications for the exploitation of S-β-CDs for drug formulation improvements or for drug delivery of anti-cancer biologics.
[1] Stutchbury, T.K., et al., Preclinical evaluation of novel, all-in-one formulations of 5-fluorouracil and folinic acid with reduced toxicity profiles. Anti-Cancer Drugs, 2011. 22(1): p. 24-34.