Preparation and evaluation of icariside II-loaded binary mixed micelles using Solutol HS15 and Pluronic F127 as carriers

Figures & data

Figure 1. (A) Chemical structure of icariside II. (B). Chemical structure of Solutol®HS15. (C). Chemical structure of Pluronics F127.

Figure 2. (A) Size distribution of SF mixed micelles as determined by DLS. (B) TEM images of SF-IS mixed micelles.

Table 1. HS15/F127 ratio and characteristics of SF mixed micelles.

HS15/F127 ratio (mg/mL)	Average size (nm)	EE (%)	Solubility (mg/mL)
20:0	13.63 ± 0.71	79.24 ± 1.66	1.14 ± 0.11
0:20	36.21 ± 1.08	68.56 ± 1.55	0.27 ± 0.06
20:20	16.66 ± 1.01	88.41 ± 1.28	1.25 ± 0.12
40:20	20.73 ± 1.56	91.42 ± 3.12	3.71 ± 0.15
60:20	13.70 ± 1.35	89.03 ± 2.75	7.22 ± 0.20
80:20	12.88 ± 0.98	94.76 ± 2.11	11.79 ± 0.34

Figure 3. In vitro release profiles of the micelles in the simulated intestinal medium, pH 6.8.

Figure 4. (A) IS. (B) SF (4:1) mixed micelles. Effects of micelles in permeability of IS (20 μM). Absorptive permeability is expressed as P_app (AP-BL) and secretory permeability is expressed as P_app (BL-AP). Date are presented as mean ± SD (n = 3). The asterisk symbol indicates a statistically significant difference. The number of asterisk symbol indicates the level of significance with **p < 0.01. One-way ANOVA with Tamhane’s post hoc was used to analyze the data statistically.

Table 2. Permeability and efflux ratio.

	Papp × 10^−6 cm/s
Compound	AP-BL	BL-AP	Efflux ratio
Icariside II	1.97 ± 0.14	15.24 ± 1.59	7.43
The mixed micelles	3.94 ± 0.65	4.82 ± 0.45	1.22

Absorption permeability was expressed as AP-BL, whereas secretory permeability was presented as BL-AP. Data expressed as mean ± SD (n = 3). Efflux radio was P_app (BL-AP)/P_app (AP-BL).

Figure 5. The plasma concentration-time curve of IS in rats after oral administration of IS, SF mixed micelles (100 mg/kg, IS). Data are presented as mean ± SD (n = 6).

Table 3. Pharmacokinetic parameters of IS, SF mixed micelles (100 mg/kg, IS).

Parameters	Icariside II	The mixed micelles
AUC0–t (μg/L*h)	3469.12 ± 749.40	8781.78 ± 413.44**
AUC0–∞ (μg/L*h)	4059.81 ± 545.56	12 886.76 ± 512.92**
MRT0–t (h)	8.421 ± 0.84	6.34 ± 0.37**
vMRT0–∞ (h)	11.60 ± 1.95	13.65 ± 0.58
t1/2 (h)	6.77 ± 1.83	13.37 ± 0.78**
Tmax (h)	1.07 ± 0.24	0.56 ± 0.45
Cmax (μg/L)	538.55 ± 109.81	2553.79 ± 399.88**

Data are presented as mean ± SD (n = 6).

** p < 0.01.

Figure 6. Gastrointestinal safety assay observed by HE staining. (A) APIs used in this study; (B) SF-IS mixed micelles used in this study (1–5) stomach and intestinal (duodenum, jejunum, ileum, colon).

Figure 7. (A) Schematic illustration of forming progress of SF-IS mixed micelles. (B) Schematic illustration of SF-IS mixed micelles inhibit the efflux system.