Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model

Abstract

Combination chemotherapy, administrating two chemotherapeutic agents concurrently, comes into prominence, as the heterogeneity or the level of the disease necessitates a collaborative action. Curcumin, isolated from turmeric, and piperine, isolated from black long pepper, are two dietary polyphenols studied for their intrinsic anti-cancer properties against various cancer types including colorectal cancer (CRC). Furthermore, piperine improves the therapeutic effect of curcumin. Addressing this mutual behavior, this study combines curcumin and piperine within emulsome nanoformulations. Curcumin-(CurcuEmulsomes) and piperine-loaded emulsomes (PiperineEmulsomes) have established a uniform, stable, spherical dispersion with average diameters of 184.21 and 248.76 nm, respectively. The solid tripalmitin inner core achieved encapsulation capacities of up to 0.10 mg/ml curcumin and 0.09 mg/ml piperine content. While piperine treatment alone-in its both free and emulsome forms-showed no inhibition in the proliferation of HCT116 cells in vitro, its presence as the second drug agent enhanced curcumin's effect. Combination of 7 µM PiperineEmulsome and 25 µM CurcuEmulsome concentrations was found to be most effective with an inhibition of cell proliferation of about 50% viability. Cell cycle arrest at G2/M phase and induced apoptosis verified the improved anti-cancer characteristics of the therapy. While CurcuEmulsomes achieved a fourfold increase in Caspase 3 level, combination of treatment with PiperineEulsomes achieved a sixfold increase in the level of this apoptotic marker. Combinational treatment of HCT116 cells with CurcuEmulsomes and PiperineEmulsomes improved the anticancer activity of the compounds and highlighted the potential of the approach for further in vivo studies.

Neuroprotective Effects of Curcumin-Loaded Emulsomes on Laser Axotomy-Induced CNS Injury Model

“…For instance, CurcuEmulsomes distinguished from emulsomes with a higher negative charge (-33.2 ± 6.7 mV), which is attributed to the contribution of molecular negative charge of curcumin to the blank formulation (-24.2 ± 6.3 mV) ( Table 1). Owing a more negative zeta potential, CurcuEmulsomes seem to distinguish from blank emulsomes (204.3 ± 20.0 nm) also with a smaller average particle size (176.8 ± 13.0 nm) as reported elsewhere [44]. The higher negative surface charge of CurcuEmulsomes are ascribed as the reason for their smaller average size in comparison to blank emulsomes.…”

“…Cell uptake analysis pointed out that CurcuEmulsomes can enter the primary hippocampal neurons within 15 minutes and localize rapidly within the membrane and inside the cytoplasm. As this is the rst study from our group reporting the use of emulsomes for delivery of neuroprotective agents into a primary neuron culture, it might be important to mention that the uptake of CurcuEmulsomes into the hippocampal neurons was observed to occur faster compared to the previously studied uptake rates of different emulsome formulations into the cancer cells such as HepG2 [43], HCT116 [44], LnCap (unpublished data) or MCF7 (unpublished data) in vitro.…”

“…CurcuEmulsome was synthesized applying the procedure described by Bolat and the colleagues [44]. Brie y, lipids including tripalmitin, dipalmitoyl phosphatidylcholine and cholesterol together with curcumin were rst dissolved in an organic solvent, i.e.…”

“…Amount of curcumin encapsulated inside CurcuEmulsomes was estimated as described elsewhere [43,44]. A 1 mg/ml stock solution of curcumin was prepared in DMSO.…”

“…synthesis/homogenization duration, temperature, mixing speed) are the other factors in uencing on the nal size of emulsomes [52]. Besides, physicochemical properties of the drug incorporated into the emulsomes seem to have an effect on both overall size and zeta potential of the formulation [44]. For instance, CurcuEmulsomes distinguished from emulsomes with a higher negative charge (-33.2 ± 6.7 mV), which is attributed to the contribution of molecular negative charge of curcumin to the blank formulation (-24.2 ± 6.3 mV) ( Table 1).…”