Abstract
Glycyrrhizic acid and its hydrolyzed metabolite 18β-glycyrrhetinic acid, obtained from the plant Glycyrrhiza glabra, have numerous pharmacological activities, such as anti-inflammatory, anti-ulcerative, antiallergic, immunomodulatory, antiviral, antitumor, hepatoprotective, and antioxidant effects, and others. In addition to the pharmacological activities, in the 1980s, an interaction and uptake of these molecules by the liver was verified, which was later confirmed by other studies through the discovery of specific receptors in the hepatocytes. The presence of these specific receptors in the liver led to vectorization and delivery of drugs, by the introduction of glycyrrhizic acid or glycyrrhetinic acid on the surface of nanosystems, for the treatment of liver diseases. This review describes experimental evidence of vectorization by conjugating glycyrrhizic acid or glycyrrhetinic acid to nanosystems and delivery of antitumor drugs for the treatment of liver cancer and also describes the techniques used to perform this conjugation. We have shown that due to the existence of specific receptors for these molecules, in addition to the targeting of nanosystems to hepatocytes, nanosystems having glycyrrhizic acid or glycyrrhetinic acid on their surface had the same therapeutic effect in a significantly lower dose compared to the free drug and unconjugated nanosystems, with consequent reduction of side effects and toxicity.
Highlights
Another type of liver cancer, but with a lower incidence, is cholangiocarcinoma, which is known as bile duct cancer; it is most commonly diagnosed in Thailand and other parts of Asia due to the presence of liver flukes in the consumed raw fish dishes [3]
GALGA-LPs (GA liposomes modified with galactosylated derivative ligand) were produced with the film dispersion method, and the results indicated that the particle size decreased when the glycyrrhetinic acid (GA)/blank liposomes proportion was optimized [73]
The in vitro experiments involving nanocarriers and different types of cells were carried out to demonstrate that the presence of GL or GA increases the cellular uptake of the formulations
Summary
In 2018, liver cancer was considered the second highest cause of male mortality with 841,080 cases diagnosed and 781,631 deaths in the same year, being the sixth highest incidence rate by age in the world [1]. Recent studies predict a rise reviewand is focused on an in-depth the research strategies to obtain in the incidence cancer by 2030 due to increased and obesity [7].able to glycyrrhizic acidof orliver glycyrrhetinic acid-conjugated drug alcoholism delivery systems that are far, the in treatment liver cancers may include hepatic resection, liver transplantatargetSo the drug the HCCofand reduce drug side effects and toxicity. GA is obtained from hydrolysis of GL, both delivery carriers for the treatment of HCC, on the basis of their hepatoprotective of them being major compounds of the Glycyrrhiza glabra L. root extract [13] It has activity exploited for over thirty years for the treatment of liver disease in Asia [10,11]. Even GA, target the drug in the HCC and reduce drug side effects when given intravenously at a dose of 240 mg three times a week for 4 weeks, is well tolerated by humans, and18β-Glycyrrhetinic it has no adverse Acid effects [16,17]
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