Cytotoxicity Studies of Free Docetaxel and Docetaxel-Loaded Nanodroplets in Human Prostate Cancer Cell Model
D Cvetkovic*, R Gupta, F Chen, L Chen, C Ma, Fox Chase Cancer Center, Philadelphia, PASU-E-U-4 Sunday 3:00PM - 6:00PM Room: Exhibit Hall
Purpose: Docetaxel is a chemotherapy drug active against a variety of solid tumors including prostate cancer. Since the clinical efficacy of docetaxel is limited by its toxicity, alternative strategies such as encapsulation in nanodroplets are needed. The purpose of this study was to compare the cytotoxicity of free docetaxel and docetaxel-loaded nanodroplets in vitro in human prostate cancer cells.
Materials and Methods: Prostate cancer LNCaP cells (5x103/well) were seeded in 96-well plates (Figure 1). After 24 hours cells adhered to the surface of the plate and were incubated with docetaxel both as free drug and loaded into nanodroplets for 3 days. Cell proliferation/cytotoxicity was evaluated by an improved form of MTT assay - WST-1 assay. The development of orange color was measured 3h after the addition of WST-1 reagent at 450nm on an Envision 2102 Multilabel Reader (Figure 2) and directly correlated to cell number. Untreated cells were used as control. The experiment was performed twice.
Results: In vitro cytotoxicity studies indicated that IC50 (the concentration of drug required for 50% inhibition of cell growth) levels of free docetaxel against LNCaP cells were from 2nM to 5nM. This finding is in agreement with in vitro data from the literature. At the same drug equivalent concentration, free docetaxel induced greater decrease in cell viability compared to encapsulated form (59, 52 and 50% vs. 88, 76 and 59% respectively at 1, 2 and 5nM) (Figure 3).
Conclusions: Our results suggested that docetaxel encapsulated in nanodroplets is less toxic than the free drug. The nanoparticles seem to protect the cells from the direct toxic effect of docetaxel. Further experiments are conducted to evaluate the effects of free and encapsulated docetaxel in vivo using an orthotopic animal prostate tumor model. The results of these studies are reported elsewhere in this meeting.