Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone-coated norcantharidin chitosan nanoparticle formulation in rats and mice, using LC-MS/MS

Figures & data

Figure 1 XRD pattern of NCTD and PVP–NCTD–NP nanoparticles.

Abbreviation: XRD, X-ray diffraction.

Figure 2 AFM ichnography of NCTD-NPs and PVP–NCTD–NPs.

Notes: 1: nanoparticles without PVP; 2: nanoparticles with PVP.

Abbreviation: AFM, atomic force microscopy.

Figure 3 AFM image of PVP–NCTD–NPs.

Table 1 Pharmacokinetic parameters of two formulations after intravenous and oral administrations to rats

Parameter	Intravenous administration (5 mg/kg)		Oral administration (5 mg/kg)
	NCTD	PVP–NCTD–NP	NCTD	PVP–NCTD–NP
AUC0-t (μg · ml^−1 · h)	9.79 ± 1.26	31.86 ± 4.42	3.85 ± 0.66	6.67 ± 1.00
AUC0-∞ (μg · ml^−1 · h)	10.77 ± 2.34	32.90 ± 4.63	3.87 ± 0.69	6.68 ± 1.08
t1/2(a) (h)	NA	NA	0.56 ± 0.43	0.80 ± 0.71
t1/2(α) (h)	0.26 ± 0.06	0.73 ± 0.14	0.72 ± 0.68	0.83 ± 0.54
t1/2(β) (h)	2.63 ± 0.82	5.99 ± 1.53	5.08 ± 4.79	6.03 ± 3.06
Cmax (μg · ml^−1)	NA	NA	1.21 ± 0.23	1.33 ± 0.31
Tmax (h)	NA	NA	1.50 ± 0.44	2.00 ± 0.52
MRT (h)	0.34 ± 0.10	0.93 ± 0.21	5.49 ± 4.58	6.53 ± 3.42
Vd (L · kg^−1)	0.82 ± 0.45	0.62 ± 0.26	9.48 ± 6.59	6.52 ± 3.87
CL (L · h^−1)	0.12 ± 0.02	0.04 ± 0.01	0.32 ± 0.05	0.19 ± 0.02
Fr	NA	325.5%	NA	173.3%

Notes: (N = 6; mean ± SD). Fr = ((AUC_{PVP–NCTD–NP} × D_NCTD)/(AUC_NCTD × D_{PVP–NCTD–NP})) × 100.

Abbreviations: SD, standard deviation; NA, not available; AUC, area under curve; t_1/2(a), half-life (minutes); t_1/2(β), half-life (hours); T, time; MRT, mean residence time; V, apparent volume of distribution; CL, clearance; Fr, relative bioavailability; D, dose.

Figure 4 Mean plasma concentration profiles of NCTD after intravenous administration of two formulations at 5 mg/kg to SD rats (N = 6).

Abbrevations: SD, Sprague-Dawley; C_NCTD, concentration of NCTD; T, time.

Figure 5 Mean plasma concentration profiles of NCTD and PVP–NCTD–NP after oral administration of 5 mg/kg to SD rats (N = 6).

Abbrevations: C_NCTD, concentration of NCTD; T, time.

Table 2 Te, RTe, and TI of NCTD and PVP–NCTD–NPs after intravenous administration

Tissue	Te		RTe	TI
	NCTD	PVP–NCTD–NPs
Blood	30.74	41.87	0.36	2.80
Heart	14.99	2.19	−0.85	0.301
Liver	10.07	5.72	−0.43	1.168
Spleen	7.44	1.86	−0.75	0.514
Lung	22.72	3.46	−0.85	0.314
Kidney	11.72	7.52	−0.36	1.321
Bile	2.33	37.39	15.05	33.03

Notes: RTe = (Te_{PVP–NCTD–NPs} − Te_NCTD)/Te_NCTD × 100%.

Abbreviations: Te, targeted efficiency; Rte, relative targeted efficiency; TI, targeted index.

Figure 6 Tissue distribution of NCTD-SOL and PVP–NCTD–NPs after intravenous administration in mice (N = 6).

Figure 7 Product ion spectra of NCTD and its metabolites in rats.

Figure 8 Structures of the main metabolites and their possible transformation in rats.

Figure 9 Cumulative amounts of excreted NCTD in urine and feces: time curves after oral administration of NCTD and PVP–NCTD–NP to rats (N = 6).