DOCETAXEL LOADED PEG-PLGA NANOPARTICLES: OPTIMIZED DRUG LOADING, IN-VITRO CYTOTOXICITY AND IN-VIVO ANTITUMOR EFFECT
2014
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) Nanoparticles (NPs) with polymer concentration (X 1 ), drug concentration (X 2 ) and ratio of the organic to aqueous solvent (X 3 ) as the independent variables and particle size (Y 1 ), poly dispersity index (PDI) (Y 2 ) and drug loading (Y 3 ) 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 Y 1 , Y 2 and Y 3 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.
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