Preparation of a nanoscale baohuoside I-phospholipid complex and determination of its absorption: in vivo and in vitro evaluations

Figures & data

Figure 1 Chemical structure of baohuoside I.

Table 1 Physicochemical properties of the baohuoside I-phospholipid complex (n = 3)

	Average size	Zeta potential
Baohuoside I-phospholipid complex (a)	227.3 ± 65.2 μm
Baohuoside I-phospholipid complex (b)	262 ± 24 nm	−18.9 ± 4.9 mV
Baohuoside I-phospholipid complex (c)	148 ± 12 nm	−19.7 ± 3.3 mV
Baohuoside I-phospholipid complex (d)	81 ± 10 nm	−17.4 ± 4.7 mV

Figure 2 Transmission electron microscopic images of baohuoside I-phospholipid complexes of different sizes. (A) 262 ± 24 nm, (B) 148 ± 12 nm, and (C) 81 ± 10 nm.

Figure 3 Chromatograms of (A) baohuoside I and (B) a nanoscale baohuoside I-phospholipid complex (81 ± 10 nm).

Figure 4 Ultraviolet spectra of (A) baohuoside I and (B) a nanoscale baohuoside I-phospholipid complex (81 ± 10 nm).

Figure 5 Differential scanning calorimetry thermograms of (A) baohuoside I, (B) the phospholipids, (C) the physical mixture, and (D) the nanoscale baohuoside I-phospholipid complex.

Figure 6 Permeability of (A) baohuoside I, (B) the baohuoside I-phospholipid complex of 262 ± 24 nm, (C) the baohuoside I-phospholipid complex of 148 ± 12 nm, and (D) the baohuoside I-phospholipid complex of 81 ± 10 nm.

Notes: The rates of transport were used to calculate the absorptive permeability [P_app (A − B)] and secretory permeability [P_app (B − A)] using Equation (1)${\text{P}}_{\text{app}}=\frac{\text{V}}{\text{S}\times \text{C}}\times \frac{\text{dC}}{\text{dt}}=\frac{1}{\text{S}\times \text{C}}\times \frac{\text{dM}}{\text{dt}}$(1) , and the calculated permeabilities are plotted here as bars. The data are expressed as the mean ± standard deviation (n = 3). *P < 0.05 baohuoside I versus the baohuoside I-phospholipid complex, with more asterisks indicating higher levels of significance (one-way analysis of variance followed by Tamhane’s post hoc test).

Table 2 Permeabilities (P_app) and efflux ratios of baohuoside I and the nanoscale baohuoside I-phospholipid complex

Compound	Papp × 10^−6 (cm/sec)		Efflux ratio
	A − B	B − A
Baohuoside I	1.85 ± 0.18	14.36 ± 0.72	7.76
Baohuoside I-phospholipid complex (262 ± 24 nm)	4.12 ± 0.34*	25.21 ± 1.49*	6.12*
Baohuoside I-phospholipid complex (148 ± 12 nm)	5.78 ± 0.86*	34.56 ± 3.77*	5.98*
Baohuoside I-phospholipid complex (81 ± 10 nm)	7.03 ± 0.96*	41.55 ± 3.53*	5.91*

Notes: The absorptive permeability was expressed as A − B, whereas the secretory permeability was expressed as B − A. The efflux ratio was P_app (B − A)/P_app (A − B). Data are presented as the mean ± standard deviation; n = 3;

* P < 0.05 versus the baohuoside I group.

Table 3 Pharmacokinetic parameters of baohuoside I, baohuoside I-phospholipid complex of 227.3 ± 65.2 μm (BPC a), baohuoside I-phospholipid complex of 262 ± 24 nm (BPC b), baohuoside I-phospholipid complex of 148 ± 12 nm (BPC c), and baohuoside I-phospholipid complex of 81 ± 10 nm (BPC d) 50 mg/kg, orally in rats (n = 6)

Parameters	Baohuoside I	BPC a	BPC b	BPC c	BPC d
AUC0–t (mg · min/L)	65.21 ± 12.29	114.37 ± 20.28*	131.39 ± 31.29*,#	154.34 ± 35.29*,#	186.81 ± 44.32*,#
AUC0–∞ (mg · min/L)	70.65 ± 14.16	146.98 ± 21.96*	179.75 ± 28.72*,#	193.84 ± 37.51*,#	242.09 ± 52.19*,#
MRT0–t (min)	471.33 ± 51.43	491.21 ± 72.14	521.49 ± 89.19	571.92 ± 98.64	641.94 ± 109.24*,#
MRT0–∞ (min)	569.58 ± 51.94	598.77 ± 68.53	659.44 ± 89.08	674.21 ± 100.23	763.78 ± 135.38*,#
Tmax (min)	53.71 ± 7.75	55.65 ± 8.22	37.32 ± 10.28*,#	32.58 ± 9.56*,#	27.13 ± 7.41*,#
Cmax (ng/mL)	296.32 ± 31.38	525.37 ± 69.45*	552.15 ± 89.92*	587.48 ± 89.92*,#	654.87 ± 89.92*,#

Notes: The data are presented as the mean ± standard deviation.

* P < 0.05 versus 50 mg/kg baohuoside I;

# P < 0.05, versus baohuoside I-phospholipid complex of 227.3 ± 65.2 μm, which contained baohuoside I 50 mg/kg.

Abbreviations: AUC, area under concentration-time curve; MRT, mean residence time; T_max, time to maximum plasma concentration; C_max, maximum plasma concentration.

Figure 7 Plasma concentration-time curve in rats after oral administration of baohuoside I and the baohuoside I-phospholipid complexes of 227.3 ± 65.2 μm, 262 ± 24 nm, 148 ± 12 nm, and 81 ± 10 nm.

Notes: The baohuoside I dose was 50 mg/kg. The data are presented as the mean ± standard deviation (n = 6).