Genkwanin nanosuspensions: a novel and potential antitumor drug in breast carcinoma therapy

Figures & data

Table 1. Characterization of GKA-NSps prepared using different stabilizer and ratios of GKA/TPGS (mean ± SD, n = 3).

Stabilizer	GKA: stabilizer	Size(nm)	PDI	Zeta potential (mV)	4 °C storage timewith similar size (h)	DLC (%)
PEG2000–PCL2000	1:1	184.7 ± 5.4	0.18 ± 0.02	−12.3 ± 1.2	60	–^a
F-127	1:1	222.7 ± 10.9	0.22 ± 0.03	−6.6 ± 2.0	24	–^a
TPGS	1:1	183.1 ± 4.4	0.16 ± 0.07	−16.2 ± 0.1	>1440	49.36 ± 0.14
TPGS	2:1	248.0 ± 8.3	0.20 ± 0.01	−15.2 ± 0.5	>576	61.29 ± 0.06
TPGS	3:1	332.3 ± 5.6	0.25 ± 0.03	−14.2 ± 0.4	>576	69.16 ± 0.21

a The data are not tested.

Figure 1. Preparation and characterization of GKA-NSps. (A) Particle size distribution and photograph of GKA-NSps; (B) TEM image of GKA-NSps; (C) XRD patterns of the GKA bulk powder, stabilizer (TPGS), GKA-NSps, and the physical mixture of GKA bulk powder and TPGS; (D) Differential scanning calorimetry thermograms of the GKA bulk powder, stabilizer (TPGS), GKA-NSps, and the physical mixture of GKA bulk powder and TPGS.

Figure 2. Stability and in vitro drug release profiles of GKA-NSps. (A) Size and PDI changes of the GKA-NSps after incubation with various physiological media at 37 °C for 12 h; (B) The in vitro drug release profiles of GKA-NSps and GKA coarse suspensions in pH 7.4 PBS containing 5% (w/v) BSA at 37 °C (mean ± SD, n = 3).

Figure 3. In vitro cytotoxicity studies and in vivo antitumor activity against MCF-7 tumor-bearing mice. (A) Cytotoxicity of GKA-NSps and GKA DMSO solution against MCF-7 cells (a) and normal HUVECs (b) after 48 h of incubation (mean ± SD, *p < .05, **p < .01); (B) (a) The growth of tumor volume with administration in each group; (b)The body weight change of mice over time (mean ± SD, n = 7, ↓represents administrating of drugs).

Table 2. IC50 values of GKA-NSps and GKA solution against different tumor cell lines and HUVECs after incubation for 48 h (mean ± SD).

IC50(μg/mL) of cancer cells	GKA-NSps	GKA DMSO solution
4T1	42.09 ± 8.83**	>100
MCF-7	2.86 ± 0.55**	9.42 ± 2.14
MDA-MB-453	52.87 ± 9.03**	>100
HeLa	7.86 ± 1.73**	25.16 ± 3.12
HepG2	12.31 ± 2.17**	>100
BT474	>100	>100
A549	3.91 ± 0.52**	14.20 ± 2.23
HUVEC	14.82 ± 2.84	14.15 ± 1.62

**p < .01 vs. GKA solution.

Table 3. Inhibiting effect of GKA-NSps in the MCF-7 model (mean ± SD, n = 7).

Formulation	Tumor weight (g)	Inhibition rate (%)
GKA-NSPs (20 mg/kg, i.v.)	0.668 ± 0.095**	53.14 ± 6.67
GKA-NSPs (40 mg/kg, i.v.)	0.647 ± 0.091**	54.60 ± 5.45
GKA-NSPs (60mg/kg, i.v.)	0.540 ± 0.106**	62.09 ± 7.45
GKA-NSPs (60 mg/kg, i.g.)	0.819 ± 0.089**,*,#	42.48 ± 6.25
PTX injection (8 mg/kg, i.v.)	0.552 ± 0.133**	61.27 ± 9.34
Free TPGS (60 mg/kg, i.v.)	1.398 ± 0.187	1.83 ± 13.13
Saline	1.424 ± 0.291	–^a

a The data are not meaningful.

*p < .05 vs. GKA-NSPs (60 mg/kg, i.v.);

**p < .01 vs. Saline;

#p < .05 vs. PTX injection (8 mg/kg, i.v.).