Preparation and characterization of novel poly(ethylene glycol) paclitaxel derivatives
| Autor: | Oddone Schiavon, Barbara Stella, Daniele Zonari, Paola Milla, Silvia Arpicco, Luigi Cattel |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Carbamate
Paclitaxel Cell Survival Drug Compounding medicine.medical_treatment Pharmaceutical Science Polyethylene Glycols chemistry.chemical_compound PEG ratio medicine Humans Organic chemistry Prodrugs Solubility Cytotoxicity PEGylation drug delivery Prodrug Antineoplastic Agents Phytogenic chemistry MCF-7 Cells HT29 Cells Ethylene glycol Conjugate |
| Zdroj: | International Journal of Pharmaceutics. 454:653-659 |
| ISSN: | 0378-5173 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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