Docetaxel Loaded PEG-PLGA Nanoparticles: Optimized Drug Loading, In-vitro Cytotoxicity and In-vivo Antitumor Effect

作者：Koopaei Mona Noori; Khoshayand Mohammad Reza; Mostafavi Seyed Hossein; Amini Mohsen; Khorramizadeh Mohammad Reza; Tehrani Mahmood Jeddi; Atyabi Fatemeh; Dinarvand Rassoul^*

来源：Iranian Journal of Pharmaceutical Research, 2014, 13(3): 819-833.

• PLGA
• Nanoparticles
• Docetaxel
• Anti-tumor
• Pegylation
• Experimental design
• Box-Behnken

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.

• 出版日期2014