Title:Development and Evaluation of a Novel Hyaluronic Acid and
Chitosan-modified Phytosome for Co-delivery of Oxymatrine and
Glycyrrhizin for Combination Therapy
Volume: 19
Issue: 2
Author(s): Xiaojin Chen, Shuying Yu, Pingping Wang, XinFeng Zhao and Gao Sang*
Affiliation:
- Department of Traditional Medicine, Hangzhou Children’s Hospital, Hangzhou, Zhejiang, 310014, China
Keywords:
Oxymatrine, glycyrrhizin, co-delivery, phytosome, multidrug resistance, cancer.
Abstract:
Background: Multidrug resistance (MDR) of cancer cells is a major obstacle to efficient
cancer chemotherapy. Combination therapy is expected to enhance the anticancer effect and
reverse MDR. Numerous patents involve different kinds of nanoparticles for the co-delivery of
multiple chemotherapeutics, but the FDA has approved none.
Objective: In this study, oxymatrine (OMT) and glycyrrhizin (GL) were co-loaded into phytosomes
as the core of nanocarriers, and the shell was cross-linked with chitosan (CS) and hyaluronic
acid (HA) with the capability for the controlled, sequential release and the targeted drug uptake.
Methods: Phospholipid complexes of OMT and GL (OGPs) were prepared by a solvent evaporation
technique and could self-assemble in an aqueous solution to form phytosomes. CS and HA
were sequentially coated on the surface of OGPs via electrostatic interactions to obtain CS coated
OGPs (CS-OGPs) and HA modified CS-OGPs (HA-CS-OGPs), respectively. The particle size and
zeta potential were measured to optimize the formulations. In vitro cytotoxicity and cellular uptake
experiments on HepG2 cells were performed to evaluate the anticancer activity.
Results: OGPs were obtained with nano-size around 100 nm, and CS and HA coating on phytosomes
could change the particle size and surface potential. The drug loading of OMT and GL
showed that the nanocarriers could maintain a fixed ratio of 1:1. The in vitro release experiments
indicated the release of OMT and GL was pH-dependent and sequential: the release of OMT from
CS-OGPs and HA-CS-OGPs was significantly increased at pH 5.0 compared to the release at pH
7.4, while GL exhibited sustained released from CS-OGPs and HA-CS-OGPs at pH 5.0. Furthermore,
in vitro cytotoxicity and cellular uptake experiments on HepG2 cells demonstrated that the
co-delivery system based on phytosomes had significant synergistic anti-tumor activities, and the
effects were enhanced by CS and HA modification.
Conclusion: The delivery of OMT and GL via HA-CS-OGPs might be a promising treatment to
reverse MDR in cancer therapy.