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.Keywords:lipase-catalytic acylation;mannose-diester lauric diacid-cholesterol;glycyrrhetinic acid liposomes;mannose receptor;liver-targeting
Fa HuanBao,Zhou JingTing,Zhang Dong,Yin Wei,Zhang HaiFeng,Huo DanQun,Hou ChangJun,Luo XiaoGang,Mao YaLi,Zhang Jin
A novel 4-(2-{[6-(1,1-dicyanoprop-1-en-2-yl)naphthalen-2-yl](methyl)amino} ethoxy)-4-oxobutanoic acid ( 5 ) fluorescent probe for β-amyloids was synthesized by catalytic acylation using 4-dimethylaminopyridine between succinic anhydride and (1-{6-[(2-hydroxyethyl)(methyl) amino]-2-naphthyl}ethylidene)malononitrile ( 4 ). The structures of all compounds were identified by proton nuclear magnetic resonance spectroscopy, infrared spectroscopy, mass spectrometry, and ultraviolet–visible (UV–Vis) spectroscopy. The UV–Vis and fluorescence spectra of 1-{6-[(2-hydroxyethyl)(methyl) amino]-2-naphthyl}ethan-1-one ( 3 ), 4 , and 5 in solvents with different polarities were investigated, and the effects of solvent polarity on the optical properties of the three compounds were studied. The objective product 5 showed high binding affinities toward Aβ(1–40) aggregates in vitro ( K
d = 29.4 nmol/L) by fluorophotometry. This study provides a powerful fluorescent probe for the molecular diagnosis of Alzheimer’s disease.
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