In vitro and in vivo studies of lipid-based nanocarriers for oral N₃-o-toluyl-fluorouracil delivery

Figures & data

Figure 1.  Chemical structure of N₃-o-toluyl-fluorouracil (TFu).

Table 1.  Physicochemical characteristics of different TFu-loaded nanocarriers.

Formulation	Mean particle size (nm)	Polydispersity index	Zeta potential (mV)	Entrapment efficiency (%)	Drug loading (%)
Cationic SLNs	178.8 ± 9.9	0.167 ± 0.018	+19.5 ± 0.3	71.0 ± 1.2	3.6 ± 0.1
Anionic SLNs	156.5 ± 0.5	0.183 ± 0.022	−30.2 ± 3.6	84.2 ± 3.6	2.1 ± 0.9
Liposomes	180.7 ± 3.9	0.093 ± 0.034	−6.56 ± 3.2	78.0 ± 4.6	7.9 ± 0.4

Each data was presented as mean ± SD, n = 3.

Figure 2.  Mean TFu blood concentrations vs time profiles after oral administration of TFu suspension, cationic TFu-SLNs, anionic TFu-SLNs, and TFu-liposomes in mice, the data were presented as mean ± SD (n = 5 in each group).

Figure 3.  Cytotoxicity of TFu-loaded nanocarriers with different concentrations after 24 h of incubation with Caco-2 cells using the CCK-8 method (compared to the negative control). Each data was presented as mean ± SD (n = 6 in each group).

Figure 4.  TFu transport across Caco-2 cell monolayers from the apical to basolateral from different formulations, the data were presented as mean ± SD (n = 6 in each group).

Figure 5.  Permeability (P_app) of TFu from free solution and three nonocarriers suspensions across the Caco-2 cell monolayers, the data were presented as mean ± SD (n = 6 in each group). * p < 0.05, ** p< 0.01 vs liposomes.

Table 2.  The absorption parameters of different formulations following in situ single-pass rat intestinal perfusion after perfusing for 6 h.

Formulations	Anionic SLNs	Cationic SLNs	Liposomes
Ka (h^−1)	0.633 ± 0.010	0.429 ± 0.078	0.337 ± 0.161
T1/2 (h)	1.096 ± 0.175	1.654 ± 0.330	2.340 ± 0.188
Uptake percentage (%)	83.25 ± 2.21	76.91 ± 1.64	69.01 ± 2.32

Each data was presented as mean ± SD (n = 5 in each group).

Table 3.  The permeability coefficient values (P_eff, cm/s) following in situ single-pass rat intestinal perfusion to the different small intestinal regions.

	Peff (cm/s)
	Duodenum	Jejunum	Ileum	Colon
Cationic SLNs	6.54 ± 0.30 × 10^−6	7.71 ± 0.49 × 10^−6	2.82 ± 0.54 × 10^−6	1.09 ± 0.29 × 10^−6
Anionic SLNs	2.69 ± 0.15 × 10^−6	5.79 ± 0.19 × 10^−6	7.11 ± 0.56 × 10^−6	2.15 ± 0.16 × 10^−6
Liposomes	3.29 ± 0.22 × 10^−6	6.16 ± 0.63 × 10^−6	4.71 ± 0.74 × 10^−6	2.44 ± 0.14 × 10^−6

Each data was presented as mean ± SD (n = 5 in each group).

Figure 6.  Absorption of drugs at various regions of the rat intestine, the data were presented as mean ± SD (n = 5 in each group). * p < 0.01 vs anionic SLNs and liposomes; ** p < 0.01 vs cationic SLNs and liposomes.