Table 7.
In vitro Studies of Nanoformulations of Bioactive Compounds of Licorice
| Formulation Type | Drug Used | Cell Line | Main Results | Reference |
|---|---|---|---|---|
| GA-alginate nanogel | Doxorubicin + Glycyrrhizin (20 mg/mL) | Murine macrophage cell line (RAW 264.7) | Activation and invasion by macrophages averted due to the presence of glycyrrhizin Cells retained the normal morphology, less nitric oxide production Reduced IL-6 and tumor necrosis factor-α expression Reduced phagocytosis of drug |
[263] |
| Hepatocellular carcinoma HepG2 cells | Confirmed pathway of endocytosis and active liver targeting which increased nanogel particle phagocytic intake Decreased cell viability and increased cell toxicity, apoptosis due to reduced efflux activity of p-glycoprotein, upregulation of caspase-3 mRNA and a high Bax/Bcl-2 ratio |
|||
| PEGylated nano-liposomes | Silibinin (25% w/v) + GA (75% w/v) (IC50 = 48.67 μg/mL) | Human hepatocellular carcinoma HepG2 cells and fibroblast cells | Decreased IC50 value and increased cytotoxicity (10x) than respective free drugs Synergistic action of silibinin in presence of GA |
[264] |
| Nano-micelles formulated as solid dispersion using tannic acid and disodium glycyrrhizin | Camptothecin (0.0145 μg/mL) | Human hepatocellular carcinoma HepG2 cells | Increased cell inhibition and cell apoptosis activity compared to free drug Tannic acid inhibited P-gp glycoprotein efflux activity thereby increasing cellular drug uptake |
[265] |
| Glycyrrhizin Conjugated Dendrimer and Multi-Walled Carbon Nanotubes | Doxorubicin (Dendrimer IC50 = 2 μM) (Nanotubes IC50 = 2.7 μM | Human hepatocellular carcinoma HepG2 cells | Reduction in IC50 value of the drug compared to formulations without glycyrrhizin and free drug Increased cytotoxicity due to increased drug intake via receptor mediated endocytosis Dendrimers (more apoptotic cells) are more effective carriers than nanotubes (more necrotic cells) when attached with glycyrrhizin |
[266] |
| GA-conjugated human serum albumin nanoparticles | Resveratrol (IC50 = 62.5 μg/mL) | Hepatocellular carcinoma HepG2 cells | Concentration dependent uptake | [267] |
| Valerate- conjugated chitosan nanoparticles surface modified with glycyrrhizin | Ferulic acid (IC50 = 60 μg/mL) | Hepatocellular carcinoma HepG2 cells | Increased cytotoxicity due to glycyrrhizin receptor mediated intake of drug | [268] |
| Glycyrrhetinic acid-modified hyaluronic acid nanoparticles | Adenine (0.25 mg/mL) | Human HepG2 cells, L02, Bel-7402 and MCF-7 cells | Absorption into HepG2 in a time dependent manner Targeting efficiency: HepG2>L02>MCF-7 Inhibition of colony formation in time and dose dependent manner Induced apoptosis in cancer cells thus inhibiting proliferation of cancer cells |
[269] |
| Glycyrrhetinic acid-modified hyaluronic acid nanoparticles | Docetaxel (IC50 = 1.6 μg/mL) | HepG2 cells and Human breast cancer MCF7 cells | More uptake by HepG2 than MCF7 cells Decrease in IC50 values and cell viability compared to free drug Inhibition of colony formation of HepG2 cells in time and dose dependent manner Increased apoptosis and deformed morphology |
[270] |
| Hyaluronic acid-glycyrrhetinic acid conjugated nanoparticles | Doxorubicin (IC50 = 5.75 μg/mL) | Hepatocellular carcinoma HepG2 cells | Increased cleavage in presence of glutathione Rapid intracellular release and nuclear delivery of drug compared to standard of care conventional formulations |
[271] |
| Glycyrrhetinic acid-modified curcumin supramolecular hydrogel | Curcumin (IC50 = 10.7 μM) | Hepatocellular carcinoma HepG2 and Mouse fibroblast 3T3 cells | Reduced IC50 values Greater targeting efficiency Higher cellular uptake due to pro-gel formulation approach |
[272] |
| Glycyrrhetinic Acid Functionalized Graphene Oxide | Doxorubicin (0.5 μg/mL) | Human hepatocellular carcinoma HepG2 cells, normal human hepatic L02 cells, and rat cardiac muscle H9c2 cells | Targeting efficiency: HepG2>L02>H9c2 Taken via endocytosis and delivered to mitochondria Decreased the potential difference of mitochondrial membrane which in turn opened up mitochondrial permeability transition pore to initiate a series of responses and leads to caspase-3 activation necessary for apoptosis |
[273] |
| Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles | Curcumin (2 mg/mL) | Hepatocellular carcinoma HepG2 cells | Higher cytotoxicity compared to curcumin loaded mesoporous silica nanoparticles Receptor mediated endocytosis intake of drug Increased rate of apoptosis |
[274] |
| Dual-functional (modified with glycyrrhetinic acid and L-histidine) hyaluronic acid nanoparticles | Doxorubicin (5 μg/mL) | Hepatocellular carcinoma HepG2 cells | Decrease in IC50 values Increased drug distribution in cytoplasm and nuclear regions Receptor mediated endocytosis intake of drug |
[275] |
| Nano-suspension | Isoliquiritigenin (0.18 μM) | A549 lung cancer cells | Increased apoptosis at 7.5 to 10-fold Less cytotoxic to healthy cells |
[276] |
| Isoliquiritigenin-iRGD nanoparticles | Isoliquiritigenin (50 μM) | Human breast cancer cell lines (MDA-MB231 and MCF7) and mouse breast cancer cell line (4T1) | MCF7 cells showed better inhibition than free drug but not better than isoliquiritigenin nanoparticles MDA-MB231 and 4T1 showed better inhibition than isoliquiritigenin nanoparticles formulation and free drug Increased apoptosis compared to free drug and nanoparticles due to high rates of cellular drug uptake |
[277] |
| Isoliquiritigenin loaded nanoliposomes | Isoliquiritigenin (<12.5 μM) | HCT116, SW620 and HT29 colorectal cancer cell lines | Better inhibition compared to free drug Increased rate of apoptosis Decreased uptake of glucose and lactic acid Reduced oxygen consumption led to reduced adenosine triphosphate synthesis Decreased Akt/mTOR expression which is important for tumor progression |
[278] |
Abbreviations: Bax, BCL2-associated X; BCL-2, B-cell lymphoma 2; GA, glycyrrhizinic acid; IC50, half maximal inhibitory concentration; mTOR, mammalian target of rapamycin; w/v, weight/volume.