Tumor microenvironment-responsive, high internal phase Pickering emulsions stabilized by lignin/chitosan oligosaccharide particles for synergistic cancer therapy.

Affiliation

Chen K(1), Qian Y(2), Wang C(3), Yang D(4), Qiu X(4), Binks BP(5).
Author information:
(1)School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China; College or Textile Science and Engineering
(International Institute of Silk), Zhejiang Sci-Tech University, Hangzhou 310018, China.
(2)School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China. Electronic address: [Email]
(3)Research Institute of Materials Science, South China University of Technology, Guangzhou 510640, China.
(4)School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.
(5)Department of Chemistry, University of Hull, Hull HU6 7RX, UK. Electronic address: [Email]

Abstract

HYPOTHESIS: The stability of anti-cancer drugs and the adverse drug reactions (ADRs) caused by drug-drug interactions (DDIs) are two major challenges of combination chemotherapy. In this work, hydrophilic drug loaded lignin-based nanoparticles were applied to stabilize high internal phase Pickering emulsions (HIPPEs) containing hydrophobic drug in the oil phase, which not only improved the stability of anti-cancer drugs, but also reduced the risk of DDIs. EXPERIMENTS: Highly biocompatible enzymatic hydrolysis lignin/chitosan oligosaccharide (EHL/COS-x) nanoparticles were prepared and used to load hydrophilic cytarabine (Ara-C). The morphology, loading capacity, encapsulation efficiency and emulsifying properties of nanoparticles were characterized and predicted. Subsequently, these nanoparticles were applied to stabilize HIPPEs with soybean oil containing hydrophobic curcumin as dispersed phase. The effects of the morphology, amphipathy and concentration of nanoparticles and oil/water ratio on the microstructure and stability of HIPPEs were investigated. Meanwhile, the controlled release, protective performance, cytotoxicity and bio-activity of HIPPEs were also evaluated. FINDINGS: EHL/COS-x nanoparticles loaded with Ara-C could stabilize HIPEs with 85 vol% soybean oil containing curcumin. The two drugs were separately loaded in same delivery system, which effectively lowered the risk of DDIs. Meanwhile, HIPPEs provided outstanding UV, thermal and oxidation protection for these two environmentally sensitive anti-cancer drugs. In addition, HIPPEs displayed a good pH-responsive release in a tumor environment. In vitro experiments show that the killing efficiency of two drugs co-loaded HIPPEs against the leukemia cell is two times higher than that of single drug loaded systems. This strategy can be extended to the synergistic therapy of two or more drugs with different physicochemical properties.