Resveratrol-loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles: Preparation, characterization, and targeting effect on liver tumors

Abstract

In this study, glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were prepared to establish a tumor targeting nano-sized drug delivery system. Glycyrrhizic acid was coupled to human serum albumin, and resveratrol was encapsulated in glycyrrhizic acid-conjugated human serum albumin by high-pressure homogenization emulsification. The average particle size of sample nanoparticles prepared under the optimal conditions was 108.1 ± 5.3 nm with a polydispersity index (PDI) of 0.001, and the amount of glycyrrhizic acid coupled with human serum albumin was 112.56 µg/mg. The drug encapsulation efficiency and drug loading efficiency were 83.6 and 11.5%, respectively. The glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were characterized through laser light scattering, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses, and gas chromatography. The characterization results showed that resveratrol in glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles existed in amorphous state and the residual amounts of chloroform and methanol in nanoparticles were separately less than the international conference on harmonization (ICH) limit. The in vitro drug-release study showed that the nanoparticles released the drug slowly and continuously. The inhibitory rate of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide method. The IC50 values of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles and resveratrol were 62.5 and 95.5 µg/ml, respectively. The target ability of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles for HepG2 cells was evaluated using fluorescence-modified albumin techniques. The uptake rate of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles was higher than that of pure resveratrol and increased with increased nanoparticles concentration. The in vivo body distribution of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles labeled with the near-infrared fluorophore Cy5 was monitored in H22 tumor-bearing mice through near-infrared fluorescence imaging systems. Glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles exhibited effective target orientation to liver tumor and sustained-release property.

Glycyrrhizic acid as a multifunctional drug carrier – From physicochemical properties to biomedical applications: A modern insight on the ancient drug

“…A lot of studies are devoted to the use of GA and its metabolite glycyrrhetic acid as a targeting unit in liver therapy Cai et al, 2016;Wu et al, 2017). As it was mentioned above, GA is effective hepatoprotective agent (see Section 4).…”

Resveratrol loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles for tail vein injection II: pharmacokinetics, tissue distribution and bioavailability

“…GL-HSA-RES-NPs was obtained by the high-pressure homogeneous emulsification method (Wu et al, 2017). Briefly, the glycyrrhizic acid (GL) of 59.6 mg was added to the methanol solution of 4.0 mL and treated in ultrasonic bath for 30 s (Li et al, 2005).…”

“…Recently, our research team reported the preparation, characterization and liver cancer targeting of glycyrrhizic acid-conjugated human serum albumin loaded RES nanoparticles (GL-HSA-RES-NPs) (Wu et al, 2017). GL-HSA-RES-NPs were prepared by a high-pressure homogeneous emulsification method with an average particle size of 108.1 ± 5.3 nm and a polydispersity index (PDI) of 0.001.…”

Resveratrol‐loaded nanomedicines for cancer applications

“…Moreover, this study also showed the beneficial effect of combining the drugs with albumin to prevent deposition of the drug at the injection site and obtain a slow release of the drug. 152…”