New Conjugates of Hyaluronic Acid with γ-Cyclodextrin as Sorafenib Carrier in Cancer Cells.

ABSTRACT

In recent years, nanoparticles based on cyclodextrins have been widely investigated, mainly for drug delivery. In this work, we synthesized nanoparticles with a hyaluronic acid backbone (11 kDa and 45 kDa) functionalized with γ-cyclodextrins. We tested sorafenib in the presence of the new hyaluronan-cyclodextrin conjugates in A2780 (ovarian cancer), SK-HeP-1 (adenocarcinoma) and MDA-MB-453 (breast cancer) cell lines. We found that hyaluronan-cyclodextrin conjugates improve the antiproliferative activity of sorafenib. Remarkably, the system based on the 11 kDa hyaluronan conjugate was the most effective and, in the MDA-MB-453 cell line, significantly reduced the IC50 value of sorafenib cells by about 75 %.