RESUMO
In this study a 3-factor, 3-level Box-Behnken design was used to prepare optimized docetaxel [DTX] loaded pegylated poly lactide-co-glycolide [PEG-PLGA] NPs with polymer concentration [X1], drug concentration [X2] and ratio of the organic to aqueous solvent [X3] as the independent variables and particle size [Y1], poly dispersity index [PDI] [Y2] and drug loading [Y3] as the responses. The cytotoxicity of optimized DTX loaded PEG-PLGA NPs was studied in SKOV3 tumor cell lines by standard MTT assay. The in vivo antitumor efficacy of DTX loaded PLGA-PEG NPs was assessed in tumor bearing female BALB/c mice. The optimum level of Y1, Y2 and Y3 predicted by the model were 188 nm, 0.16 and 9% respectively with perfect agreement with the experimental data. The in vitro release profile of optimum formulation showed a burst release of approximately 20% [w/w] followed by a sustained release profile of the loaded drug over 288 h. The DTX loaded optimized nanoparticles showed a greater cytotoxicity against SKOV3 cancer cells than free DTX. Enhanced tumor-suppression effects were achieved with DTX-loaded PEG-PLGA NPs. These results demonstrated that optimized NPs could be a potentially useful delivery system for DTX as an anticancer agent