Improved delivery of Mcl-1 and survivin siRNA combination in breast cancer cells with additive siRNA complexes.

This study aimed at investigating the influence of commercial transfection reagents (Prime-Fect, Leu-Fect A, and Leu-Fect C) complexed with different siRNAs (CDC20, HSP90, Mcl-1 and Survivin) in MDA-MB-436 breast cancer cells and the impact of incorporating an anionic additive, Trans-Booster, into siRNA formulations for improving in vitro gene silencing and delivery efficiency. Gene silencing was quantitatively analyzed by real-time RT-PCR while cell proliferation and siRNA uptake were evaluated by the MTT assay and flow cytometry, respectively. Amongst the investigated siRNAs and transfection reagents, Mcl-1/Prime-Fect complexes showed the highest inhibition of cell viability and the most effective siRNA delivery. The effect of various formulations on transfection efficiency showed that the additive with 1:1 ratio with siRNA was optimal achieving the lowest cell viability compared to untreated cells and negative control siRNA treatment (p < 0.05). Furthermore, the combination of Mcl-1 and survivin siRNA suppressed the growth of MDA-MB-436 cells more effectively than treatment with the single siRNAs and resulted in cell viability as low as ~ 20% (vs. non-treated cells). This aligned well with the induction of apoptosis as analyzed by flow cytometry, which revealed higher apoptotic cells with the combination treatment group. We conclude that commercial transfection reagents formulated with Mcl-1/Survivin siRNA combination could serve as a potent anti-proliferation agent in the treatment of breast cancers.

Diffusion Modeling and In Vitro Release Kinetics Studies of Curcumin-Loaded Superparamagnetic Nanomicelles in Cancer Drug Delivery System.

The purpose of this study was to investigate in vitro drug release kinetics and to develop diffusion model of curcumin loaded Pluronic F127/Oleic acid(OA)-Fe3O4 nanoparticles. The prepared superparamagnetic nanoparticles by co-precipitation technique were characterized by the average size, size distribution, crystallinity, colloidal stability and magnetic property. The release of curcumin was triggered by an acidic environment in pH 5.0 of phosphate buffer saline. Release data of various curcumin loading (15, 25 and 30 ppm) were fitted using non-linear first-order, second-order, Higuchi and Korsmeyer-Peppas model. All the curcumin release mechanism followed Korsmeyer-Peppas model with n values less than 0.45 indicating the Fickian diffusion of curcumin from the prepared nanomicelles. The dynamic of controlled drug release of dilute curcumin loading was well described by a combination of diffusion and first-order release rate. The corresponding diffusion coefficient and kinetic rate were 9.1 × 10-7 cm2⋅min-1 and 6.51 × 10-7 min-1, which were used as controlled release to achieve the desired curcumin constant release rate in the delivery system.