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. 2018 Sep;16(3):1639-1646.
doi: 10.3892/etm.2018.6416. Epub 2018 Jul 6.

Preparation and characterization of norcantharidin liposomes modified with stearyl glycyrrhetinate

Jing Zhu  1 , Wei Zhang  1 , Dandan Wang  1 , Suzhen Li  2 , Wei Wu  1
Affiliations

Preparation and characterization of norcantharidin liposomes modified with stearyl glycyrrhetinate

Jing Zhu et al. Exp Ther Med. 2018 Sep.

Abstract

In the current study, norcantharidin (NCTD)-loaded liposomes (LIPs) modified with stearyl glycyrrhetinate (SG; SG-NCTD-LIP) were prepared by the ethanol injection method. To increase the drug encapsulation efficiency (EE), the formulation of NCTD-LIP was optimized by single factor test and orthogonal design. The release of NCTD in vitro from SG-NCTD-LIP was evaluated by equilibrium dialysis. The cytotoxicity of SG-NCTD-LIP in HepG2 was investigated by MTT assay. The results revealed that the EE of liposomes was ~27.80%, the average SG-NCTD-LIP was 87.5 nm, the in vitro NCTD release from SG-NCTD-LIP was delayed compared with NCTD in solution and the drug-release kinetic followed a first-order model. MTT assays revealed increased cytotoxicity activity against HepG2 cells for SG-NCTD-LIP compared with free NCTD. In conclusion, SG-NCTD-LIP prepared in the present study may be a promising liposomal drug delivery system for anticancer drugs in liver-targeting therapy.

Keywords: drug delivery system; liposomes; liver-targeting; norcantharidin; stearyl glycyrrhetinate.

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Figures

Figure 1.
Figure 1.
Chemical structure of norcantharidin.
Figure 2.
Figure 2.
Chemical structure of stearyl glycyrrhetinate.
Figure 3.
Figure 3.
Ethanol injection method for preparation of SG-NCTD-LIP. The ethanol phase, containing EPC, cholesterol and SG in ethanol, was injected into the aqueous phase, containing NCTD dissolved in PBS, and incubated stirring for 30 min to yield SG-NCTD-LIP. EPC, egg phosphatidylcholine; SG, stearyl glycyrrhetinate; NCTD, norcantharidin; SG-NCTD-LIP, NCTD-loaded liposomes modified with SG.
Figure 4.
Figure 4.
Effect of different preparation variables on the EE of SG-NCTD-LIP. Effect of changes in (A) phospholipid concentration (static parameters: 1:5 NCTD-phospholipid mass ratio and 1:7 cholesterol-phospholipid mass ratio at an incubation temperature of 50°C), (B) NCTD-phospholipid mass ratio (static parameters: 0.24% Phospholipid concentration, 1:7 cholesterol-phospholipid mass ratio at an incubation temperature of 50°C), (C) cholesterol-phospholipid mass ratio (static parameters: 0.24% Phospholipid concentration, 1:20 NCTD-phospholipid mass ratio at an incubation temperature of 50°C) and (D) incubation temperature (static parameters: 0.24% Phospholipid concentration, 1:20 NCTD-phospholipid mass ratio and 1:5 cholesterol-phospholipid mass ratio) on EE. EE, encapsulation efficiency; NCTD, norcantharidin.
Figure 5.
Figure 5.
Particle size distribution (intensity) and TEM image of norcantharidin-loaded liposomes modified with stearyl glycyrrhetinate. TEM, transmission electron microscopy.
Figure 6.
Figure 6.
In vitro release of NCTD from solution and SG-NCTD-LIP over time. NCTD, norcantharidin; SG-NCTD-LIP, NCTD-loaded liposomes modified with stearyl glycyrrhetinate; Q, cumulative release percentage. *P<0.05 vs. SG-NCTD-LIP.
Figure 7.
Figure 7.
Inhibitory effects of different concentrations of NCTD in solution, NCTD-LIP and SG-NCTD-LIP on HepG2 cells after 48 h. ⋆P<0.05 vs. NCTD solution; ▲P<0.05 vs. NCTD-LIP. NCTD, norcantharidin; LIP, liposome; NCTD-LIP, NCTD-loaded liposomes, SG-NCTD-LIP, NCTD-loaded LIPs modified with stearyl glycyrrhetinate; IR, inhibition ratio.
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