Silicate esters of paclitaxel and docetaxel: synthesis, hydrophobicity, hydrolytic stability, cytotoxicity, and prodrug potential

Wohl, A. R.; Michel, A. R.; Kalscheuer, S.; Macosko, C. W.; Panyam, J.; Hoye, T. R. J. Med. Chem. 201457, 2368–2379.

"We report here the synthesis and selected properties of various silicate ester derivatives (tetraalkoxysilanes) of the taxanes paclitaxel (PTX) and docetaxel (DTX) [i.e., PTX-OSi(OR)3 and DTX-OSi(OR)3]. Both the hydrophobicity and hydrolytic lability of these silicates can be (independently) controlled by choice of the alkyl group (R). The synthesis, structural characterization, hydrolytic reactivity, and in vitro cytotoxicity against the MDA-MB-231 breast cancer cell line of most of these derivatives are described. We envision that the greater hydrophobicity of these silicates (vis-à-vis PTX or DTX itself) should be advantageous from the perspective of preparation of stable aqueous dispersions of amphiphilic block-copolymer-based nanoparticle formulations."