Development and Evaluation of a Novel Hyaluronic Acid and Chitosan-modified Phytosome for Co-delivery of Oxymatrine and Glycyrrhizin for Combination Therapy.
Xiaojin Chen, Shuying Yu, Pingping Wang, XinFeng Zhao, Gao Sang
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引用次数: 0
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.
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Aims & Scope
Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.
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