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Hepatitis B, one of the most common contagious viral hepatitis with high infection rate, is challenging to treat. Although the treatment for hepatitis B has been improved over the years, many therapeutic drugs still have either severe adverse effects or insufficient effectiveness via systemic administration. In this study, we confirmed that glycyrrhetinic acid can enhance the accumulation of entecavir in HepaRG cell and liver. Then we constructed a novel albumin nanoparticle co-loading entecavir and glycyrrhetinic acid (ETV-GA-AN) to improve liver accumulation of entecavir and investigated its ability to deliver both drugs to liver. In vitro cellular uptake study and in vivo tissue distribution experiment show that these negatively charged ETV-GA-AN (112 ± 2 nm in diameter) can increase the accumulation of entecavir in hepatic HepaRG cells and improve entecavir distribution in liver. We also revealed the mechanism that glycyrrhetinic acid enhances intracellular accumulation of entecavir by inhibiting the activity of specific efflux transporters. Our delivery system is the first liver-targeted albumin nanoparticle that utilizes the site-specific co-delivery strategy to delivery entecavir and glycyrrhetinic acid. As it combines high efficiency and low toxicity, it possess great potential for treating hepatitis B.
This article was published in the following journal.
Name: Molecular pharmaceutics
Cancer is one of the most abundant causes of death in the world due to its characteristic features such as indefinite growth of cells, invasion of healthy tissues, and also metastasis. Conventional tr...
Albumin is a promising surface modifier of nanoparticulate drug delivery systems. Serving as a dysopsonin, albumin can protect circulating nanoparticles (NPs) from the recognition and clearance by the...
In this study, promising approaches of dual-targeted micelles and drug-polymer conjugation were combined to enable injection of poorly soluble anti-cancer drugs together with site-specific drug releas...
Herein, we reported a glycyrrhetinic acid (GA)-decorated small molecule conjugate for pH-triggered near infra-red (NIR) fluorescence imaging of hepatocellular carcinoma (HCC). Our ''in vitro'' studies...
Understanding the transcytosis phenomenon through albumin binding receptor (glycoproteins) is an important step towards targeted drug delivery research. The transcytosis of bovine serum albumin (BSA) ...
Patients who have completed 2-years entecavir-based treatment in Regress Study will receive another 5-years entecavir extension therapy. Patients will be assessed at baseline and every six...
In this study we aim to investigate to what extent the serum albumin concentration in liver transplant patients treated with mycophenolic acid (MPA) affect the free fraction of MPA. Furthe...
This clinical observational cohort study assess the loss of albumin from blood circulation during and after liver transplantation by mass balance of albumin. The overall assumption of this...
The purpose of the study is to examine if outcome after liver transplantation is improved by using albumin infusion post-transplantation.
The purpose of this clinical research study is to learn if the study drug entecavir will prevent the recurrence of hepatitis B virus in subjects who receive an orthotopic liver transplant ...
A condition in which albumin level in blood (SERUM ALBUMIN) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (ALBUMINURIA).
An oleanolic acid from GLYCYRRHIZA that has some antiallergic, antibacterial, and antiviral properties. It is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation.
Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.
A widely used anti-inflammatory agent isolated from the licorice root. It is metabolized to GLYCYRRHETINIC ACID, which inhibits 11-BETA-HYDROXYSTEROID DEHYDROGENASES and other enzymes involved in the metabolism of CORTICOSTEROIDS. Therefore, glycyrrhizic acid, which is the main and sweet component of licorice, has been investigated for its ability to cause hypermineralocorticoidism with sodium retention and potassium loss, edema, increased blood pressure, as well as depression of the renin-angiotensin-aldosterone system.
Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...