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

Abstract

BackgroundThe 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.ResultsWe 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.ConclusionsMost 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.

Prevention of Breast Cancer by Natural Phytochemicals: Focusing on Molecular Targets and Combinational Strategy

“…Among them, polymer and lipid‐based nanocarriers and pH‐susceptible delivery systems have emerged as a promising tool to deal with the route of administration and distribution on drug action . An example in breast cancer treatments, quercetin and curcumin in combination with a chemotherapeutic drug through a specific delivery system offered effective antitumor capability via enhancing oral bioavailability, targeting cellular uptake efficiency, and controlling drug specifically release at tumor cell . Another interesting aspect of the dietary supplementation of phytochemicals prevent breast carcinogenesis is possibly their ability to influence gastrointestinal tract and breast tissue microbiota activities .…”

<p>Traditional Chinese medicine-combination therapies utilizing nanotechnology-based targeted delivery systems: a new strategy for antitumor treatment</p>

“…Alemi et al 234 loaded both Cur and Ptx into cationic PEGylated niosomal formulations using thin-film hydration method to enhance efficacy in MCF7 human breast adenocarcinoma cells. The combination of Ptx and Cur, particularly in the nanoniosome formulations, improved the effectiveness of cancer therapy.…”

<p>Liver-targeted liposomes for codelivery of curcumin and combretastatin A4 phosphate: preparation, characterization, and antitumor effects</p>

“…Cellular uptake of liposomal formulations was evaluated in BEL7402 cell by qualitative methods. 41 Cells (5×10 3 ) were seeded onto a glass-bottom cell-culture dish (ϕ20 mm) and incubated for 24 hours at 37°C until adherent growth was observed. After incubation with FITC LPs or FITC-GA LPs (2.4 mg/mL) for 30 minutes, all reagents were removed and cells washed in cold PBS (pH 7.4) three times, fixed with 4% polyformaldehyde for 10 minutes, and stained with DAPI (0.1 µg/mL, diluted with PBS) for 5 minutes in the CO 2 incubator.…”