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Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy

Authors :
Ashraf Alemi
Javad Zavar Reza
Fateme Haghiralsadat
Hossein Zarei Jaliani
Mojtaba Haghi Karamallah
Seyed Ahmad Hosseini
Somayeh Haghi Karamallah
Source :
Journal of Nanobiotechnology, Vol 16, Iss 1, Pp 1-20 (2018)
Publication Year :
2018
Publisher :
BMC, 2018.

Abstract

Abstract Background The systemic administration of cytotoxic chemotherapeutic agents for cancer treatment often has toxic side effects, limiting the usage dose. To increase chemotherapeutic efficacy while reducing toxic effects, a rational design for synergy-based drug regimens is essential. This study investigated the augmentation of therapeutic effectiveness with the co-administration of paclitaxel (PTX; an effective chemotherapeutic drug for breast cancer) and curcumin (CUR; a chemosensitizer) in an MCF-7 cell line. Results We optimized niosome formulations in terms of surfactant and cholesterol content. Afterward, the novel cationic PEGylated niosomal formulations containing Tween-60: cholesterol:DOTAP:DSPE-mPEG (at 59.5:25.5:10:5) were designed and developed to serve as a model for better transfection efficiency and improved stability. The optimum formulations represented potential advantages, including extremely high entrapment efficiency (~ 100% for both therapeutic drug), spherical shape, smooth-surface morphology, suitable positive charge (zeta potential ~ + 15 mV for both CUR and PTX), sustained release, small diameter (~ 90 nm for both agents), desired stability, and augmented cellular uptake. Furthermore, the CUR and PTX kinetic release could be adequately fitted to the Higuchi model. A threefold and 3.6-fold reduction in CUR and PTX concentration was measured, respectively, when the CUR and PTX was administered in nano-niosome compared to free CUR and free PTX solutions in MCF-7 cells. When administered in nano-niosome formulations, the combination treatment of CUR and PTX was particularly effective in enhancing the cytotoxicity activity against MCF-7 cells. Conclusions Most importantly, CUR and PTX, in both free form and niosomal forms, were determined to be less toxic on MCF-10A human normal cells in comparison to MCF-7 cells. The findings indicate that the combination therapy of PTX with CUR using the novel cationic PEGylated niosome delivery is a promising strategy for more effective breast cancer treatment.

Details

Language :
English
ISSN :
14773155
Volume :
16
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Nanobiotechnology
Publication Type :
Academic Journal
Accession number :
edsdoj.1a3754fdb4f140228552ed0103dbef11
Document Type :
article
Full Text :
https://doi.org/10.1186/s12951-018-0351-4