In vitro and in vivo evaluation of macromolecular prodrug GC-FUA based nanoparticle for hepatocellular carcinoma chemotherapy

Figures & data

Figure 1. Size distribution of GC-FUA-NPs (A), and release profile of the GC-FUA-NPs and 5-Fu loaded GC nanoparticles in PBS (n = 3, B), and transmission electron microscope (TEM) image of GC-FUA nanoparticles (C).

Figure 2. BSA adsorbance incubated with GC-FUA-NPs and free 5-Fu at different times (A), and percentage of red blood cell hemolysis incubated with GC-FUA-NPs (B).

Figure 3. In vitro cell inhibition of 5-Fu and GC-FUA-NPs in HepG2 at different times (A) 24 h and (B) 48 h, and in A549 at different times (C) 24 h and (D) 48 h (n = 3, p > 0.05 versus 5-Fu).

Table 1. IC₅₀ of 5-Fu and GC-FUA-NPs in HepG2 and A549 cells (A), and pharmacokinetic parameters of 5-Fu and GC-FUA-NPs administration to SD rats (n = 3, B).

A
		IC50 (mmol/l)
Drug	Time(h)	HepG2	A549
5-Fu	24	0.701 ± 0.023	0.672 ± 0.042
	48	0.662 ± 0.022	0.601 ± 0.037
GC-FUA  nanoparticles	24	0.238 ± 0.021^a	0.498 ± 0.035
	48	0.147 ± 0.017^a	0.433 ± 0.031
B
Parameter	5-Fu	GC-FUA-NPs
T1/2 (h)	0.55	40.55
AUC0–t (μg/ml·h)	153.99	326.91
AUC0–∞ (μg/ml·h)	155.31	651.00
CL (μg/(μg/ml)/h)	44.00	11.46
VSS (μg/(μg/ml))	41.62	528.43

^ap < 0.05 versus 5-Fu.

Figure 4. In vitro cell uptake of the FUA and GC-FUA-NPs against (n = 3, A), and galactose incubation cells uptake of the FUA and GC-FUA-NPs by HepG2 and A549 cells (n = 3, B).

Figure 5. Mean 5-Fu concentration–time curves in plasma after tail vein i.v. injection of free 5-Fu and GC-FUA-NPs to SD rats (n = 3, A), and biodistribution of free 5-Fu (B) and GC-FUA-NPs (C) in tissue (n = 3).