Pharmacokinetics and tissue distribution of docetaxel liposome mediated by a novel galactosylated cholesterol derivatives synthesized by lipase-catalyzed esterification in non-aqueous phase

Figures & data

Table 1. Standard curves, correlation coefficient and linear range of DOC in plasma and tissues of mice.

Plasma or tissue	Linear equation	r^2	Linear range (ng/mL)
Plasma of rat	Y = 3.4252X + 0.2114	0.9995	3.25–26 000
Plasma of mice	Y = 3.4471X + 0.2996	0.9999	3.25–13 000
Heart	y = 3.3037x + 0.2231	0.9994	3.25–13000
Liver	Y = 3.5921X + 0.0556	0.9997	3.25–13 000
	Y = 3.6136X + 0.1846	0.9999	13–26 000
Spleen	Y = 3.3037X + 0.2375	0.9994	3.25–13 000
Lung	Y = 3.2533X + 0.1088	0.9998	3.25–13 000
Kidney	Y = 3.5947X + 0.0146	0.9996	3.25–13 000

Table 2. The inter-(n = 5) and intra (n = 5)-day precision and recovery of the method for determination of DOC in plasma and tissues samples.

Biological matrix	QC (μg/mL)	Intra-day (n = 5) precision (RSD, %)	Inter-day (n = 5) precision (RSD, %)	Recovery (mean ± SD, %)
	0.013	2.435	6.024	97.84 ± 9.36
Plasma	6.5	2.669	3.802	88.35 ± 10.89
	13	4.864	4.294	101.91 ± 3.60
	0.013	5.738	3.403	103.32 ± 8.19
Heart	6.5	3.641	2.904	100.42 ± 17.17
	13	4.193	13.183	98.70 ± 8.88
	0.013	2.594	11.093	95.67 ± 10.75
Liver	6.5	2.789	14.23	96.63 ± 4.08
	13	2.409	6.132	100.87 ± 4.17
	0.013	9.401	6.289	88.16 ± 14.78
Spleen	6.5	3.121	8.987	97.58 ± 7.81
	13	3.074	11.284	103.99 ± 14.47
	0.013	12.131	5.237	87.29 ± 12.54
Lung	6.5	4.143	2.986	98.17 ± 7.25
	13	4.478	7.274	102.04 ± 10.37
	0.013	11.667	10.29	91.57 ± 8.48
Kidney	6.5	4.722	8.283	97.59 ± 10.05
	13	5.407	9.283	93.67 ± 14.54

Table 3. Entrapment efficiency, particle size and zeta-potential of freshly prepared liposome suspensions.

Type of liposomes	EE (%)	Particle size (nm)	Zeta-potential (mV)
DOC-L	73.6 ± 2.9	92.8	22.54
G-DOC-L	76.8 ± 3.5	95.6	27.19

Table 4. Pharmacokinetic parameters of DOC-i, DOC-L and G-DOC-L in rat plasma following intravenous administration (n = 5).

Parameters	DOC-i	DOC-L	G-DOC-L
AUC0–∞  (μg h L^−1)	1677.76 ± 270.99	2608.37 ± 813.46	683.51 ± 260.88*
MRT0–∞ (h)	4.06 ± 0.48	4.24 ± 1.29	3.24 ± 4.48
t1/2z (h)	4.35 ± 0.68	2.97 ± 1.13	3.39 ± 4.90
CL (L h^−1kg^−1)	1.52 ± 0.24	1.09 ± 0.48	4.19 ± 1.80*
Vd (L kg^−1)	9.57 ± 2.47	4.04 ± 1.00	15.92 ± 16.82*

*p < 0.05 versus DOC-i and DOC-L.

Figure 1. Mean plasma concentration of DOC in rat after i.v. administration of DOC-i, DOC-L and G-DOC-L at dose to 2.5 mg/kg of DOC (mean ± SD; n = 5).

Figure 2. Concentration–time profile of DOC in heart (A), liver (B), spleen (C), lung (D), kidney (E) and plasma (F) of mice after i.v. administration of DOC-i, DOC-L and G-DOC-L at dose to 3.5 mg/kg of DOC (n = 5).

Figure 3. Concentration of DOC in heart (A), liver (B), spleen (C), lung (D), kidney (E) and plasma (F) of mice at various time points after i.v. administration of DOC-i, DOC-L and G-DOC-L at dose to 3.5 mg/kg of DOC (n = 5).

Table 5. Pharmacokinetic parameters of DOC-i, DOC-L and G-DOC-L in plasma and various tissues of mice after intravenous administration (n = 5).

	AUC0–240 (mg h L^−1)			Cmax (mg L^−1)
Tissues	DOC-i	DOC-L	G-DOC-L	DOC-i	DOC-L	G-DOC-L
Plasma	5.018	7.829	6.576	5.201	7.359	6.930
Heart	2.176	2.157	1.500	2.141	1.268	0.763
Liver	7.900	0.741	35.846	7.028	0.779	23.831
Spleen	1.835	0.981	4.365	1.542	0.946	4.056
Lung	5.668	9.798	11.880	4.841	5.169	9.826
Kidney	11.880	2.587	4.991	8.053	2.940	2.725

Table 6. The Te (%) of DOC-i in plasma and various tissues of mice.

Parameter	Plasma	Heart	Liver	Spleen	Lung	Kidney
Te (%)	17.88	7.75	26.01	6.54	20.19	21.64

Table 7. Targeting parameters of DOC-L in plasma and various tissues of mice.

Parameters	Plasma	Heart	Liver	Spleen	Lung	Kidney
Re	1.560	0.991	0.102	0.533	1.730	0.426
Te (%)	32.500	8.950	3.080	4.060	40.670	10.740
RTe	1.818	1.155	0.118	0.621	2.014	0.496
Ce	1.415	0.592	0.111	0.613	1.068	0.365

Table 8. Targeting parameters of G-DOC-L in plasma and various tissues of mice.

Parameters	Plasma	Heart	Liver	Spleen	Lung	Kidney
Re	1.311	0.689	4.011	2.379	2.091	0.822
Te (%)	10.090	2.300	55.010	6.700	18.230	7.660
RTe	0.565	0.297	2.115	1.025	0.903	0.354
Ce	1.332	0.356	3.391	2.630	2.029	0.338