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Title: Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer cells
Authors: Wanisa Punfa
Supachai Yodkeeree
Pornsiri Pitchakarn
Chadarat Ampasavate
Pornngarm Limtrakul
Keywords: Medicine
Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jun-2012
Abstract: Aim: To compare the anti-cancer activity and cellular uptake of curcumin (Cur) delivered by targeted and non-targeted drug delivery systems in multidrug-resistant cervical cancer cells. Methods: Cur was entrapped into poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Cur-NPs) in the presence of modified-pluronic F127 stabilizer using nano-precipitation technique. On the surface of Cur-NPs, the carboxy-terminal of modified pluronic F127 was conjugated to the amino-terminal of anti-P-glycoprotein (P-gp) (Cur-NPs-APgp). The physical properties of the Cur-NPs, including particle size, zeta potential, particle morphology and Cur release kinetics, were investigated. Cellular uptake and specificity of the Cur-NPs and Cur-NPs-APgp were detected in cervical cancer cell lines KB-V1 (higher expression of P-gp) and KB-3-1 (lower expression of P-gp) using fluorescence microscope and flow cytometry, respectively. Cytotoxicity of the Cur-NPs and Cur-NPs-APgp was determined using MTT assay. Results: The particle size of Cur-NPs and Cur-NPs-APgp was 127 and 132 nm, respectively. The entrapment efficiency and actual loading of Cur-NPs-APgp (60% and 5 g Cur/mg NP) were lower than those of Cur-NPs (99% and 7 μg Cur/mg NP). The specific binding of Cur-NPs-APgp to KB-V1 cells was significantly higher than that to KB-3-1 cells. Cellular uptake of Cur-NPs-APgp into KB-V1 cells was higher, as compared to KB-3-1 cells. However, the cellular uptake of Cur-NPs and Cur-NPs-IgG did not differ between the two types of cells. Besides, the cytotoxicity of Cur-NPs-APgp in KB-V1 cells was higher than those of Cur and Cur-NPs. Conclusion: The results demonstrate that Cur-NPs-APgp targeted to P-gp on the cell surface membrane of KB-V1 cells, thus enhancing the cellular uptake and cytotoxicity of Cur. © 2012 CPS and SIMM All rights reserved.
ISSN: 17457254
Appears in Collections:CMUL: Journal Articles

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