The influence of bile salt on the chemotherapeutic response of docetaxel-loaded thermosensitive nanomicelles

Figures & data

Table 1 Rheological properties of DCT-loaded nanomicelles without or with 0.1% NaTC

Properties	Without NaTC	With NaTC
Gelation temperature (°C)	33.0±0.5	34.2±0.6
Viscosity at 25°C (mPa·s)	192.0±2.0	162.0±3.0
Gel strength (×10^2 mPa·s)	252.0±1.0	234.0±1.0
Gelation time (minutes)	2.0	2.9
Mucoadhesive force (×10^2 dyne/cm^2)	18.5±1.7	17.3±2.3

Note: Each value represents the mean ± standard deviation (n=3).

Abbreviations: DCT, docetaxel; NaTC, sodium taurocholate.

Figure 1 Schematic illustration of the preparation of DCT-loaded nanomicelles containing NaTC.

Figure 2 (A) TEM image of DCT-loaded nanomicelles containing NaTC. (B) Optical images of DCT-loaded nanomicelles at room temperature (liquid; a,b) and biological temperature (solid; c,d). Images correspond to nanomicelles without (a,c) and with NaTC (b,d).

Abbreviations: TEM, transmission electron microscope; DCT, docetaxel; NaTC, sodium taurocholate.

Figure 3 Rheological behavior of DCT-loaded nanomicelles for rectal administration at 36.5°C.

Abbreviations: DCT, docetaxel; NaTC, sodium taurocholate.

Figure 4 Plasma concentration-time profiles of DCT-loaded nanomicelles with and without NaTC in rats after rectal administration.

Notes: The DCT-loaded nanomicelle with NaTC was composed of DCT/P407/P188/Tween 80/NaTC (0.25%/11%/15%/10%/0.1%). IV DCT solution was used as a control and each value represents the mean ± standard deviation (n=6). *Significantly higher than plain nanomicelle group (P<0.05).

Abbreviations: DCT, docetaxel; NaTC, sodium taurocholate; IV, intravenous; Na, sodium.

Table 2 Pharmacokinetic parameters of rectally administered DCT-loaded nanomicelles (without or with 0.1% NaTC) and intravenous DCT solution at a dose of 5 mg/kg

Parameters	Rectal, without NaTC	Rectal, with 0.1% NaTC	Intravenous
AUC (h·ng/mL)	2,940.8±783.5	3,405.8±614.7	10,393.0±1377.2
Tmax (h)	1.17±0.29	1.67±0.29	–
Cmax (ng/mL)	739.5±143.2	808.2±92.9	10,316.3±1717.6
T1/2 (h)	1.49±0.46	2.47±0.58	0.89±0.17
Kel (h^−1)	0.50±0.15	0.29±0.08	0.80±0.15
Absolute bioavailability (%)	28.3	32.8	–

Note: Each value represents the mean ± standard deviation (n=6).

Abbreviations: DCT, docetaxel; NaTC, sodium taurocholate; AUC, area under the whole blood concentration-time curve; h, hour; T_max, time to reach maximum plasma concentration; C_max, maximum plasma concentration; T_1/2, half life; K_el, elimination rate constant.

Figure 5 Anti-tumor efficacy of DCT-loaded nanomicelles with and without NaTC after rectal administration.

Notes: Each value represents the mean ± standard deviation (n=7). *Significantly smaller than control group (P<0.01).

Abbreviations: DCT, docetaxel; NaTC, sodium taurocholate.

Figure 6 Body weight changes of tumor-bearing nude mice after rectal administration of DCT-loaded nanomicelles with and without NaTC.

Note: Each value represents the mean ± standard deviation (n=7).

Abbreviations: DCT, docetaxel; NaTC, sodium taurocholate.