Lim, Jongdoo and Lo, Su-Tang and Hill, Sonia and Pavan, Giovanni Maria and Sun, Xiankai and Simanek, Eric E (2012) Antitumor activity and molecular dynamics simulations of paclitaxel-laden triazine dendrimers. Molecular pharmaceutics, 9 (3). pp. 404-412. ISSN 1543-8384
Full text not available from this repository.Abstract
The antitumor activities of triazine dendrimers bearing paclitaxel, a well-known mitotic inhibitor, are evaluated in SCID mice bearing human prostate cancer xenografts. To increase the activity of a first generation prodrug 1 that contained twelve paclitaxel molecules tethered via an ester linkage, the new construct described here, prodrug 2, tethers paclitaxel with linkers containing both an ester and disulfide. While PEGylation is necessary for solubility, and may improve biocompatibility and increase plasma half-life, it increases the heterogeneity of the sample with an average of eight to nine PEG chains (2 kDa each) incorporated. The heterogeneous population of PEGylated materials was used without fractionation based on models obtained from molecular dynamics simulations. Three models were examined; hexaPEGylated, nonaPEGylated, and dodecaPEGylated constructs. Intravenous delivery of prodrug 2 was performed by single, double or triple dosing regimes with doses spaced by one week. The doses varied from 50 mg of paclitaxel/kg to 200 mg of paclitaxel/kg. Tumor growth arrest and regression was observed over the 10-week treatment period without mortality for mice treated with the 50 mg of paclitaxel/kg treated three times.
| Item Type: | Scientific journal article, Newspaper article or Magazine article |
|---|---|
| Uncontrolled Keywords: | dendrimer; drug delivery; molecular dynamics; paclitaxel; prostate cancer; simulation; triazine; xenografts |
| Subjects: | Physical sciences > Chemistry |
| Depositing User: | Giovanni Maria Pavan |
| Date Deposited: | 23 Aug 2016 07:16 |
| Last Modified: | 23 Aug 2016 07:16 |
| URI: | http://repository.supsi.ch/id/eprint/7621 |
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