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Iran J Pharm Res. 2014 Summer;13(3):819-33.

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

Author information

1
Novel Drug Delivery Lab, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran. ; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
2
Department of Drug and Food Control, Faculty of Pharmacy and Pharmaceutical Quality Assurance Research Center , Tehran University of Medical Sciences, Tehran, Iran.
3
Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
4
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
5
Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran.
6
Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Abstract

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 (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.

KEYWORDS:

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

PMID:
25276182
PMCID:
PMC4177642

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