PLoS One. 2016 Dec 9;11(12):e0167787. doi: 10.1371/journal.pone.0167787. eCollection 2016.
- 1Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
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.
