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Paper Information

Journal:   IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)   2014 , Volume 13 , Number 3; Page(s) 819 To 833.
 
Paper: 

DOCETAXEL LOADED PEG-PLGA NANOPARTICLES: OPTIMIZED DRUG LOADING, IN-VITRO CYTOTOXICITY AND IN-VIVO ANTITUMOR EFFECT

 
 
Author(s):  NOORI KOOPAEI MONA, KHOSHAYAND MOHAMMAD REZA, MOSTAFAVI SEYED HOSSEIN, AMINI MOHSEN, KHORRAMIZADEH MOHAMMAD REZA, JEDDI TEHRANI MAHMOOD, ATYABI FATEMEH, DINARVAND RASSOUL*
 
* NOVEL DRUG DELIVERY LAB, FACULTY OF PHARMACY, TEHRAN UNIVERSITY OF MEDICAL SCIENCES, TEHRAN 1417614411, 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.

 
Keyword(s): PLGA, NANOPARTICLES, DOCETAXEL, ANTI-TUMOR, PEGYLATION, EXPERIMENTAL DESIGN, BOX-BEHNKEN
 
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