Abstract
Mannose-diester lauric diacid-cholesterol (Man-DLD-Chol), as a liposomal target ligand, was synthesized by lipase catalyzed in a non-aqueous medium. Its chemical structure was confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Glycyrrhetinic acid (GA) liposomes containing Man-DLD-Chol (Man-DLD-Chol-GA-Lp) were prepared by the film-dispersion method. We evaluated the characterizations of liposomes, drug-release in vitro, the hemolytic test, cellular uptake, pharmacokinetics, and the tissue distributions. The cellular uptake in vitro suggested that the uptake of Man-DLD-Chol-modified liposomes was significantly higher than that of unmodified liposomes in HepG2 cells. Pharmacokinetic parameters indicated that Man-DLD-Chol-GA-Lp was eliminated more rapidly than GA-Lp. In tissue distributions, the targeting efficiency (Te) of Man-DLD-Chol-GA-Lp on liver was 54.67%, relative targeting efficiency (RTe) was 3.39, relative uptake rate (Re) was 4.78, and peak concentration ratio (Ce) was 3.46. All these results supported the hypothesis that Man-DLD-Chol would be an efficient liposomal carrier, and demonstrated that Man-DLD-Chol-GA-Lp has potential as a drug delivery for liver-targeting therapy.
Highlights
Liver diseases can be caused by various factors that damage the liver
The mean residence time (MRT0-∞) of Man-diester lauric diacid (DLD)-Chol-Glycyrrhetinic acid (GA)-Lp was the the shortest (1.35 ± 0.05 h). These results indicated that Man-DLD-Chol-GA liposomes (GA-Lp) was eliminated more shortest (1.35 ± 0.05 h)
These results indicated that Man-DLD-Chol-GA-Lp was eliminated more rapidly rapidly than GA-Lp and GA solution (GA-S) from the blood circulation system
Summary
Liver diseases can be caused by various factors that damage the liver. There are four major liver diseases, including fatter liver, cirrhosis, hepatitis, and hepatocellular carcinoma, while the latter two belong to serious public health issues [1,2,3]. According to 2015 cancer statistics, the incidence of hepatocellular carcinoma was fourth in all cancers and its mortality rate was the third highest in. Most conventional anti-tumor drugs for treatment of hepatocellular carcinoma have little or no specificity, which results in systemic toxicity, causing undesirable side effects [5]. A drug delivery system targeting hepatic cells would be an attractive approach to cure hepatic diseases.
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