Chen Kai, Qian Yong, Wang Chaoyang, Yang Dongjie, Qiu Xueqing, Binks Bernard P
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.
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.
J Colloid Interface Sci. 2021 Jun;591:352-362. doi: 10.1016/j.jcis.2021.02.012. Epub 2021 Feb 10.
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.
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.
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.
抗癌药物的稳定性以及药物相互作用（DDIs）引起的药物不良反应（ADRs）是联合化疗的两大挑战。在本研究中，负载亲水性药物的木质素基纳米颗粒被用于稳定油相中含有疏水性药物的高内相比Pickering乳液（HIPPEs），这不仅提高了抗癌药物的稳定性，还降低了药物相互作用的风险。
制备了具有高度生物相容性的酶解木质素/壳寡糖（EHL/COS-x）纳米颗粒，并用于负载亲水性阿糖胞苷（Ara-C）。对纳米颗粒的形态、负载量、包封率和乳化性能进行了表征和预测。随后，将这些纳米颗粒用于稳定以含有疏水性姜黄素的大豆油为分散相的HIPPEs。研究了纳米颗粒的形态、两亲性和浓度以及油/水比对HIPPEs微观结构和稳定性的影响。同时，还评估了HIPPEs的控释性能、保护性能、细胞毒性和生物活性。
负载Ara-C的EHL/COS-x纳米颗粒可以稳定含有85体积%姜黄素的大豆油的HIPEs。两种药物分别负载在同一递送系统中，有效降低了药物相互作用的风险。同时，HIPPEs为这两种对环境敏感的抗癌药物提供了出色的紫外线、热和氧化保护。此外，HIPPEs在肿瘤环境中表现出良好的pH响应释放。体外实验表明，共负载两种药物的HIPPEs对白血病细胞的杀伤效率比单负载药物的系统高两倍。该策略可扩展到两种或更多种具有不同理化性质的药物的协同治疗。
