pgp - publications

Predict more pgp - ligand interactions now!

1. Acta Pharmacol Sin. 2012 May 14. doi: 10.1038/aps.2012.34. [Epub ahead of print]

Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA
nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer

Punfa W, Yodkeeree S, Pitchakarn P, Ampasavate C, Limtrakul P.

Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang
Mai 50200, Thailand.

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 μg 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.

PMID: 22580738 [PubMed - as supplied by publisher]