Injectable hydrogels based on glycyrrhizin, alginate, and calcium for three‐dimensional cell culture in liver tissue engineering

Xiao-fang, Tong; Zhao, Fa-Quan; Ren, Ying-Zong; Zhang, Yi; Cui, Yuan‐Lu; Wang, Qiang-Song

doi:10.1002/jbm.a.36528

Cited by 46 publications

(21 citation statements)

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“…In a recent study, both glycyrrhizin (GL) and DOX were encapsulated into alginate (ALG) nanogel particles via the phase inversion temperature emulsification method; the obtained drug-loaded alginate nanogels (DOX/GL-ALG NGPs) exhibited not only the hepatocellular carcinoma targeting property by GL, but also the synergistic antitumor effects of GL and DOX ( Figure 9) [107]. In addition, ALG nanogels also presented favorable biocompatibility and low toxicity to hepatic tissues by controlled drug release [108]. These studies also implied that nanogels are an ideal nanoplatform for combination therapy.…”

Section: Combinational Chemotherapymentioning

confidence: 99%

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

et al. 2020

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Nanogel-based nanoplatforms have become a tremendously promising system of drug delivery. Nanogels constructed by chemical crosslinking or physical self-assembly exhibit the ability to encapsulate hydrophilic or hydrophobic therapeutics, including but not limited to small-molecule compounds and proteins, DNA/RNA sequences, and even ultrasmall nanoparticles, within their 3D polymer network. The nanosized nature of the carriers endows them with a specific surface area and inner space, increasing the stability of loaded drugs and prolonging their circulation time. Reactions or the cleavage of chemical bonds in the structure of drug-loaded nanogels have been shown to trigger the controlled or sustained drug release. Through the design of specific chemical structures and different methods of production, nanogels can realize diverse responsiveness (temperature-sensitive, pH-sensitive and redox-sensitive), and enable the stimuli-responsive release of drugs in the microenvironments of various diseases. To improve therapeutic outcomes and increase the precision of therapy, nanogels can be modified by specific ligands to achieve active targeting and enhance the drug accumulation in disease sites. Moreover, the biomembrane-camouflaged nanogels exhibit additional intelligent targeted delivery features. Consequently, the targeted delivery of therapeutic agents, as well as the combinational therapy strategy, result in the improved efficacy of disease treatments, though the introduction of a multifunctional nanogel-based drug delivery system.

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Section: Combinational Chemotherapymentioning

confidence: 99%

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

et al. 2020

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“…Hence, scaffolds fabricated by 3D printing hold new promise in creating functional liver tissues [127]. Recently, an injectable hydrogel made from glycyrrhizin (GL), alginate (Alg), and calcium (Ca) was designed for application in LTE, and the GL–Alg–Ca hydrogel could maintain proliferation and liver specific functions of a hepatic cell line [128].…”

Section: Hydrogels For Ltementioning

confidence: 99%

Hydrogels for Liver Tissue Engineering

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Penning

et al. 2019

Bioengineering

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Bioengineered livers are promising in vitro models for drug testing, toxicological studies, and as disease models, and might in the future be an alternative for donor organs to treat end-stage liver diseases. Liver tissue engineering (LTE) aims to construct liver models that are physiologically relevant. To make bioengineered livers, the two most important ingredients are hepatic cells and supportive materials such as hydrogels. In the past decades, dozens of hydrogels have been developed to act as supportive materials, and some have been used for in vitro models and formed functional liver constructs. However, currently none of the used hydrogels are suitable for in vivo transplantation. Here, the histology of the human liver and its relationship with LTE is introduced. After that, significant characteristics of hydrogels are described focusing on LTE. Then, both natural and synthetic materials utilized in hydrogels for LTE are reviewed individually. Finally, a conclusion is drawn on a comparison of the different hydrogels and their characteristics and ideal hydrogels are proposed to promote LTE.

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“…Although GL or GA by polymer-drug conjugate to construct the targeting delivery system showed active liver targeting effect, the immunoregulatory and anti-inflammatory effects of GL or GA were decreased dramatically by steric hindrance effect. Moreover, our recent study showed that the injectable GL-ALG hydrogels existed good biological activity for three-dimensional cell culture in liver tissue engineering 18.…”

Section: Introductionmentioning

confidence: 99%

Co-delivery of glycyrrhizin and doxorubicin by alginate nanogel particles attenuates the activation of macrophage and enhances the therapeutic efficacy for hepatocellular carcinoma

et al. 2019

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Nanocarrier drug delivery systems (NDDS) have been paid more attention over conventional drug delivery system for cancer therapy. However, the efficacy is hampered by the fast clearance of activated macrophage from the blood circulation system. In this study, glycyrrhizin (GL) was introduced into alginate (ALG) nanogel particles (NGPs) to construct multifunctional delivery vehicle to decrease the fast clearance of activated macrophage and enhance the anticancer efficacy with the combination therapy of GL and doxorubicin (DOX).Methods: We firstly synthesized the GL-ALG NGPs with intermolecular hydrogen bond and ionic bond as the multifunctional delivery vehicle. The immune response and phagocytosis of macrophage on GL-ALG NGPs were investigated on RAW 264.7 macrophages. The pharmacokinetic study of DOX loaded in GL-ALG NGPs was performed in rats. The active targeting effects of GL-ALG NGPs were further studied on hepatocellular carcinoma cell (HepG2) and H22 tumor-bearing mice. Moreover, the anticancer molecular mechanism of DOX/GL-ALG NGPs was investigated on HepG2 cells in vitro and tumor-bearing mice in vivo.Results: GL-ALG NGPs could not only avoid triggering the immuno-inflammatory responses of macrophages but also decreasing the phagocytosis of macrophage. The bioavailability of DOX was increased about 13.2 times by DOX/GL-ALG NGPs than free DOX in blood. The mice with normal immune functions used in constructing the tumor-bearing mice instead of the nude mouse also indicated the good biocompatibility of NGPs. GL-mediated ALG NGPs exhibited excellent hepatocellular carcinoma targeting effect in vitro and in vivo. The results suggested that the anticancer molecular mechanism of the combination therapy of glycyrrhizin and doxorubicin in ALG NGPs was performed via regulating apoptosis pathway of Bax/Bcl-2 ratio and caspase-3 activity, which was also verified in H22 tumor-bearing mice.Conclusion: DOX/GL-ALG NGPs could attenuate the activation of macrophage and enhance the therapeutic efficacy for hepatocellular carcinoma. Our results suggest that the combination therapy would provide a new strategy for liver cancer treatment.

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Injectable hydrogels based on glycyrrhizin, alginate, and calcium for three‐dimensional cell culture in liver tissue engineering

Cited by 46 publications

References 50 publications

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

Hydrogels for Liver Tissue Engineering

Co-delivery of glycyrrhizin and doxorubicin by alginate nanogel particles attenuates the activation of macrophage and enhances the therapeutic efficacy for hepatocellular carcinoma

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