title: Preparation and characterization of novel poly(ethylene glycol) paclitaxel derivatives.
abstract: Paclitaxel has been found to be very effective against several human cancers; one of the major problems with its use is its poor solubility, which makes necessary its solubilization with excipients that can determine allergic reactions often severe. The aim of this study is to develop highly water-soluble prodrugs of paclitaxel. For this purpose we prepared a series of new paclitaxel-poly(ethylene glycol) (PEG) conjugates that were characterized and evaluated for their in vitro stability and cytotoxicity. In particular, in order to modulate the release of paclitaxel from prodrugs, we prepared different compounds introducing PEG in the drug C2' and/or C7 positions via ester or carbamate linkage. The conjugates were obtained in high purity and good yield. The carbamate prodrugs were highly stable in different media, while the compounds obtained linking PEG at C2' position through an ester bond showed lower stability. Finally, the cytotoxic activity of the conjugates was evaluated on two cancer cell lines and the results showed that all the derivatives had a reduced cytotoxicity compared to that of paclitaxel.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, Via Pietro Giuria 9, 10125 Torino, Italy. silvia.arpicco@unito.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Arpicco
authors.forename: Barbara
authors.initials: B
authors.lastname: Stella
authors.forename: Oddone
authors.initials: O
authors.lastname: Schiavon
authors.forename: Paola
authors.initials: P
authors.lastname: Milla
authors.forename: Daniele
authors.initials: D
authors.lastname: Zonari
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattel
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: Paclitaxel; Poly(ethylene glycol); Prodrugs; Stability