Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer

Abstract

Ginsenoside compound K (CK) is one of the effective ingredients in antitumor composition of ginsenoside. However, the poor water solubility and significant efflux have limited the widespread clinical use of CK. In this study, preparation of novel CK-loaded d -alpha-tocopheryl polyethylene glycol 1,000 succinate/poly(ethylene glycol)-poly(ε-caprolactone) mixed micelles (CK-M) is discussed to solve the above problems. Particle size, zeta potential, and morphology were characterized using dynamic light scattering and transmission electron microscopy. CK-M are spherical shaped with an average particle size of 53.07±1.31 nm with high drug loading of 11.19%±0.87% and entrapment efficiency of 94.60%±1.45%. Water solubility of CK was improved to 3.78±0.09 mg/mL, which was ~107.35 times higher than free CK. A549 and PC-9 cells were used to evaluate in vitro cytotoxicity and cellular uptake. IC 50 values of CK-M in A549 and PC-9 cells (24 h) were 25.43±2.18 and 18.35±1.90 μg/mL, respectively. Enhanced cellular uptake of CK-M was observed in both cells. Moreover, CK-M promoted tumor cell apoptosis, inhibited tumor cell invasion, metastasis, and efflux through regulation of Bax, Bcl-2, matrix metalloproteinase-2, Caspase-3, and P-glycoprotein. In vivo imaging indicated that CK-M has excellent tumor targeting effect within 24 h, and the relative tumor inhibition rate of CK-M was 52.04%±4.62% compared with control group ( P <0.01). Thus, CK-M could be an appropriate delivery agent for enhanced solubility and antitumor effect of CK.

Ginsenoside CK induces apoptosis and suppresses proliferation and invasion of human osteosarcoma cells through the PI3K/mTOR/p70S6K1 pathway

“…Ginsenoside CK, a major member of the originally reported ginseng diol saponin, has been a topic of research in the fields of anti-inflammatory and antitumor effects. Recent studies have revealed that ginsenoside CK has anti-inflammatory, antioxidative, and neuroprotective effects (13)(14)(15)(16), and of particular interest are its antitumor effects.…”

Pharmacokinetics and Intestinal Metabolism of Compound K in Rats and Mice

“…The use of nanocrystals for PPD formulation improved oral bioavailability and brain delivery [15]. The use of the metabolism inhibitor piperine [20] in the formulation of PPD and the use of P-gp inhibitor, α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) [21], in the formulation of PPD and compound K enhanced oral absorption and anticancer efficacy of these PPD and compound K [22,23]. These approaches may provide a strategy for developing formulations for compound K and PPD by modulating their pharmacokinetic features.…”

<p>Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy</p>

“…The critical micelle concentration (CMC) of TPGS-Solutol was determined by a pyrene fluorescence method. 31 The characterization of the PHTSm including particle size distribution, polydispersity index (PDI), and zeta potential were measured by a Zetasizer (Nano ZS90; Malvern Panalytical, Malvern, UK). Its morphology was observed through a transmission electron microscope (TEM) and atomic force microscopy (AFM).…”