title: Silicate esters of paclitaxel and docetaxel: synthesis, hydrophobicity, hydrolytic stability, cytotoxicity, and prodrug potential.
abstract: 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.
authors.affiliation: Departments of †Chemistry, ‡Pharmaceutics, and §Chemical Engineering and Materials Science, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Wohl
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Michel
authors.forename: Stephen
authors.initials: S
authors.lastname: Kalscheuer
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Macosko
authors.forename: Jayanth
authors.initials: J
authors.lastname: Panyam
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hoye
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D000077143:Docetaxel; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D007202:Indicators and Reagents; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D053758:Nanoparticles; D017239:Paclitaxel / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D017640:Silicates / Q000138:chemical synthesis* / Q000494:pharmacology*; D043823:Taxoids / Q000138:chemical synthesis* / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D007202:Indicators and Reagents; D011355:Prodrugs; D017640:Silicates; D043823:Taxoids; D013778:Tetrazolium Salts; D013844:Thiazoles; D000077143:Docetaxel; C022616:thiazolyl blue; D017239:Paclitaxel