Long-Circulating Curcumin-Loaded Liposome Formulations with High Incorporation Efficiency, Stability and Anticancer Activity towards Pancreatic Adenocarcinoma Cell Lines In Vitro

Abstract

The incorporation of hydrophobic drugs into liposomes improve their bioavailability and leads to increased stability and anticancer activity, along with decreased drug toxicity. Curcumin (Cur) is a natural polyphenol compound with a potent anticancer activity in pancreatic adenocarcinoma (PA). In the present study, different types of Cur-loaded liposomal formulations were prepared and characterized in terms of size, shape, zeta potential, optimal drug-to-lipid ratio and stability at 4°C, 37°C; and in human plasma in vitro. The best formulation in terms of these parameters was PEGylated, cholesterol-free formulation based upon hydrogenated soya PC (HSPC:DSPE-PEG2000:Cur, termed H5), which had a 0.05/10 molar ratio of drug-to-lipid, was found to be stable and had a 96% Cur incorporation efficiency. All Cur-loaded liposomal formulations had potent anticancer activity on the PA cancer cell lines AsPC-1 and BxPC-3, and were less toxic to a normal cell line (NHDF). Furthermore, apoptosis-induction induced by Cur in PA cells was associated with morphological changes including cell shrinkage, cytoplasmic blebbing, irregularity in shape and the externalization of cell membrane phosphatidylserine, which was preceded by an increase in intracellular reactive oxygen species (ROS) generation and caspase 3/7 activation. Because the liposomal formulations tested here, especially the H5 variant which exhibited slow release of the Cur in the human plasma test, the formulation may be stable enough to facilitate the accumulation of pharmacologically active amounts of Cur in target cancer tissue by EPR. Therefore, our formulations could serve as a promising therapeutic approach for pancreatic cancer and other cancers.

Easy-to-perform and cost-effective fabrication of continuous-flow reactors and their application for nanomaterials synthesis

“…Conversely, the size of liposomes stored at 25°C was almost unchanged over time. Moreover, the zeta potential of liposomes produced using the 3DPM-C/Tape rector (at FRR of 25 and TFR of 1 ml/min) was -15.06 mV, which is coherent with the literature [27].…”

Bioactivity, Health Benefits, and Related Molecular Mechanisms of Curcumin: Current Progress, Challenges, and Perspectives

“…Curcumin has exhibited anticancer effects via inducing apoptosis in a variety of cancers. The apoptosis induced by curcumin leads to the morphological alternations of cancer cells, including cell shrinkage, cytoplasmic blebbing, irregularity in shape, and externalization of cell membrane phosphatidylserine [ 88 ]. The apoptosis mechanism of curcumin involves certain biomolecules and several signal pathways [ 89 ].…”

Curcumin induces apoptosis in trophoblast model cell line

“…These results were consistent with those of previous studies showing that curcumin inhibits the anti-apoptotic protein and regulates the pro-apoptotic protein. 23 The inhibitors of NF-κB expose the cancer cells to apoptosis. 24 A previous study reported that the administration of 100 pg of 17-β estradiol could increase NF-κB expression in CMH trophoblast cells cultures.…”