Characterization of ginsenoside compound K loaded ionically cross-linked carboxymethyl chitosan–calcium nanoparticles and its cytotoxic potential against prostate cancer cells

Abstract

Backgroud Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo . This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK–OCMC Nps), which enhance the aqueous solubility and stability of GK. Methods The GK–OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK–OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK–OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK–OCMC Nps. Results The GK–OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK–OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK–OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK–OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9. Conclusion GK–OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

“…In a recent comparative study on CK and CK within OCMC NPs showed that the later had higher water solubility and membrane permeability [ 42 ]. Similarly, a recent study found that CK-loaded with A54-PEG-DA-OCMC, known as APD-CK micelles, enhanced the delivery of CK.…”

“… ↑cytotoxicity for A549 and HT29 compared to CK ↑apoptosis after laser treatment in AGS [ 40 ] CK + chitosan NPs In vitro HepG2 cells CK and CK-NPs (3.125, 6.25, 12.5, 25, and 30 μg/mL), 24 h At 30 μg/mL, the apoptotic cell percentage, CK (39.02 ± 0.42%) and CK-NPs (47.57 ± 1.65%) [ 41 ] GK-OCMC NPs In vitro PC3 cells CK and GK-OCMC NPs (30 μg/mL) ↑ apoptosis by GK-OCMC treatment ↑ levels of caspase-3 (29.93%) and caspase-9 (20.78%) compared to GK treatment. [ 42 ] APD-CK micelles In vitro HepG2 and Huh-7 cells CK (30, 20, 10, 5, and 2.5 μg/mL), 24 h and 48 h Time-dependent and dose-dependent cytotoxic effects of APD-CK ↑expressions of PARP, caspase-3, and -9 in HepG2 cells by APD-CK micelles [ 43 ] Parthenolide/ CK tLyp-1 liposomes In vivo Nude mice 5 mg/kg, 24 h Strong tumor inhibition with parthenolide/ CK tLyp-1 liposomes than combined [ 91 ] In vitro A549 Parthenolide (1.5 µg/mL) + CK (30 µg/mL) in 5:1 ratio ↑ mitochondrial apoptosis: CK (8.2%), parthenolide (11.8%), CK+ parthenolide (34.7%), Parthenolide/ CK tLyp-1 liposomes (56.7%) ↑ROS levels: CK (3.7%), parthenolide (5.8%), CK+ parthenolide (24.6%), Parthenolide/ CK tLyp-1 liposomes (28.7 %) Marked structural changes in mitochondria and impaired mitochondrial membrane potential …”

“…Authors described a lower (IC 50 = 16.58 μg/mL) value for CK-NPs compared to CK (IC 50 = 23.33 μg/mL) in HepG2 cells [ 41 ]. Likewise, CK loaded O-OCMC nanoparticles showed inhibitory effects against prostate cancer (PC3) cells through enhanced cytotoxicity and uptake of CK [ 42 ]. Chitosan polymer micelles decorated using A54 peptide, known as APD-CK, were utilized against Huh-7 and HepG2 cells.…”

Anticancer properties and pharmaceutical applications of ginsenoside compound K: A review

“…A new study discovered that CK-loaded ionically crosslinked carboxymethyl chitosan-calcium nanoparticles enhance the water solubility and permeability, thereby increasing the cytotoxicity and cellular uptake of CK toward prostate cancer cells (Zhang et al, 2021).…”

Construction of Ginsenoside Nanoparticles with pH/Reduction Dual Response for Enhancement of Their Cytotoxicity Toward HepG2 Cells

“…17,18 At present, research on the construction of nanodrug delivery systems for the delivery of ginsenosides (such as ginsenoside compound K) has been reported. 19 However, the results of clinical trials show that the traditional polymer nanocarriers may not be able to achieve the programmed release of drugs in pathological changes, resulting in multiple drug resistance of cells and reduced efficacy. 20 Meanwhile, because of the simple physical encapsulation and the instability of the carrier in vivo, the drug can easily leak out of the nanocarrier in the systemic circulation, which leads to serious side effects.…”