The Effect of Polyamidoamine Dendrimers on the In Vitro Cytotoxicity of Paclitaxel in Cultured Prostate Cancer (PC-3M) Cells
Paclitaxel (Taxol™) (PTX) is an anticancer drug that has been approved for the treatment of various cancers. A major problem with developing PTX as a chemotherapeutic agent is its poor aqueous solubility. The aim of the present study was to investigate the effect of polyamidoamine dendrimers on the aqueous solubility and in vitro cytotoxicity of PTX. Solubility studies of PTX were carried out in the presence of G-3 and G-5 PAMAM dendrimers at 30 °C using the traditional rotary bottle method. In the presence of G-3-dendrimer, the solubility of PTX increased linearly with increasing dendrimer concentrations, whereas a negative deviation from linearity was observed at higher concentrations of the G-5-dendrimer. The solubility of PTX was increased from 4.83 × 10−6 M to 71.89 × 10−6 M (15 fold) and to 511.28 × 10−6 M (109 fold) by G-3 and G-5-dendrimers, respectively. PTX release from the dendrimer complexes was comparable to that from Taxol. In vitro cytotoxicity of PTX and PTX-dendrimer complexes against a cultured prostate cancer cell line (PC-3M) was studied from changes in cell proliferation, immunofluorescence of cytoskeletal organization, and nuclear condensation. Compared to the PTX treated cells, PTX-dendrimer treated cells showed marked morphological differences in cell shape and size, along with enhanced apoptosis. The enhanced cytotoxicity of PTX-dendrimer complexes could be due to the increased solubility of the drug and/or cellular uptake of PTX-dendrimer complexes by the PC-3M cells. However, much remains to be learned concerning the nature of the observed effects.
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Document Type: Research Article
Publication date: 2007-12-01
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