Improved oral absorption and anti-lung cancer activity of paclitaxel-loaded mixed micelles

Figures & data

Figure 1. Size distribution of PTX-TP-M (panel A); TEM micrographs of PTX-TP-M (panel B); schematic illustration of the structure of PTX-TP-M (panel C). Scale bar = 100 nm.

Table 1. Characteristics of PTX-loaded mixed micelle system.

TPGS:PVPS630 (mg/mL:mg/mL)	Average size (nm)	PDI	DL%	EE%	Solubility (mg/mL)
100:50	83.5 ± 1.8	0.265 ± 0.007	3.09 ± 0.09	95.67 ± 2.84	4.78 ± 0.14

Data are presented as mean ± SD (n = 3).

Figure 2. In vitro PTX release profiles from PTX-loaded mixed micelles and free drug at 37 °C over 48 h. Data are expressed as mean ± SD (n = 3).

Figure 3. Schematic illustration of PTX-TP-M inhibits the efflux system and contributes to absorption.

Table 2. Permeability and efflux ratio of PTX and PTX-TP-M.

	Papp × 10^−6 cm/s
Group	AP-BL	BL-AP	Efflux ratio
PTX	0.92 ± 0.11	41.24 ± 2.10	44.83
PTX-TP-M	4.33 ± 0.41*	15.26 ± 1.58*	3.52

Absorption permeability was expressed as AP-BL, whereas secretory permeability was presented as BL-AP. Efflux ratio was P_{app (BL-AP)}/P_{app (AP-BL)}. Data expressed as mean ± SD (n = 3).

* Significant difference compared to PTX (p < 0.01).

Figure 4. The plasma concentration-time curve of PTX in rats after oral administration of PTX, PTX-loaded mixed micelles (20 mg/kg, IS). Data are presented as mean ± SD (n = 6).

Table 3. Pharmacokinetic parameters of PTX and PTX-TP-M (20 mg/kg, PTX).

Parameters	PTX	PTX-TP-M
AUC0–t (μg/L × h)	481.70 ± 84.18	2579.45 ± 306.32*
AUC0–∞ (μg/L × h)	676.08 ± 294.78	2640.68 ± 399.84*
MRT0–t (h)	6.94 ± 1.30	6.27 ± 0.41
MRT0–∞ (h)	14.46 ± 6.46	6.79 ± 0.55*
t1/2 (h)	10.21 ± 5.03	3.35 ± 1.72*
Tmax (h)	1.08 ± 0.38	3.33 ± 0.58*
Cmax (μg/L)	131.14 ± 23.55	446.04 ± 76.75*

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

* Significant difference compared to PTX (p < 0.01).

Table 4. IC₅₀ values against A549 and Lewis cells after 24-h treatment.

	IC50 (μg/mL)
Cell line	PTX	PTX-TP-M
A459	5.21 ± 0.93	3.14 ± 0.85*
Lewis	14.53 ± 1.96	8.28 ± 1.02*

Data are presented as mean ± SD (n = 6). *Significant difference compared to PTX (p < 0.01).

Figure 5. Tumor volumes of C57BL/6 mice implanted with Lewis cells in control, PTX, PTX-TP-M groups (panel A). The results are presented as the mean ± SD (n = 6); pathological section images of the tumor tissues of control and Lewis tumor-bearing C57BL/6 mice treated by PTX and PTX-TP-M (panel B). Scale bar = 20 or 50 μm.

Figure 6. Gastrointestinal safety assay observed by H&E staining. (S) Stomach and (I) Intestine.