Self-assembled drug delivery system based on low-molecular-weight bis-amide organogelator: synthesis, properties and in vivo evaluation

Figures & data

Table 1. The response values for the different levels of experimental design.

Run	X1 (mg)	X2 (mL)	X3 (mg)	Y24h (%)	Y15d (%)
1	80.00	0.10	10.00	21.13	62.83
2	50.00	0.20	10.00	24.57	75.04
3	50.00	0.20	10.00	24.38	72.61
4	50.00	0.20	10.00	26.33	75.54
5	50.00	0.30	15.00	25.95	68.10
6	80.00	0.20	15.00	21.28	60.28
7	20.00	0.20	15.00	29.12	77.21
8	80.00	0.20	5.00	30.58	89.20
9	50.00	0.30	5.00	30.27	101.45
10	50.00	0.20	10.00	24.21	75.04
11	20.00	0.20	5.00	36.44	100.12
12	50.00	0.10	15.00	20.09	69.10
13	20.00	0.30	10.00	28.72	97.48
14	80.00	0.30	10.00	22.83	66.98
15	50.00	0.20	10.00	24.62	77.86
16	20.00	0.10	10.00	23.04	75.73
17	50.00	0.30	5.00	28.60	81.68

X₁, X₂, X₃ – different amounts of MDP, NMP, and CC.

Y_24h and Y_15d represent the drug release percent at 24 h and 15 d.

Table 2. Minimal gelator concentration of MDP in different solvent at 25 °C.

Solution	MGC (g/L)	Solution	MGC (g/L)	Solution	MGC (g/L)
Injectable soybean oil	3.3	Cyclohexane	96.5	Ethylene glycol	–
Corn oil	4.5	Tetrachloromethane	125.0	Acetonitrile	20.8
MCT	6.3	Toluene	166.7	Ethanol	51.7
Sunflower oil	7.2	Dimethylbenzene	–	Methanol	50.0
Olive oil	4.4	Chloroform	–	DMSO	13.2
Blend oil	3.6	p-Dioxane	–	Heptane	50.0

“–”means value higher than 200.

Figure 1. Phase transition temperature of the organogel based on MDP. (A) Temperature of sol to gel (T_sg) and (B) temperature of gel to sol (T_gs).

Scheme 1. The synthetic scheme of methyl (S)-2,5-ditetradecanamidopentanoate.

Figure 2. SEM images of xerogels formed by MDP in toluene at the concentration of 10% (A) and 15% (B).

Figure 3. DSC thermograms of the drug (A) and organogel (B) with (a), (d) CC organogel and (b), (c) blank organogel.

Figure 4. Variation of storage modulus (G′) and loss modulus (G″) of blank organogel (A) and CC organogel (B).

Figure 5. Calibration curve of electrical conductivity with NMP in PBS.

Figure 6. Electrical conductivity curves of organogel without NMP (▪) and organogel contained NMP (•).

Figure 7. In vitro release profiles of oil solution (•) and organogel formulation (▪).

Figure 8. In vivo plasma concentration–time curves of drug oily solution (▪) and organogel formulation (•).

Table 3. Pharmacokinetic parameters obtained after subcutaneous injection of oily solution and organogel formulation in rats (mean ± SD; n = 5).

Formulations	Cmax (μg/mL)	Tmax (h)	t1/2 (h)	AUC0-∞ (μg/mL/h)
Oily solution	20.48 ± 0.52	2 ± 0.50	6.50 ± 1.69	192.05 ± 25.56
CC organogel	16.07 ± 1.45	5.2 ± 1.79	45.627 ± 21.06	561.67 ± 119.38

Figure 9. In vivo cumulative release-time curve of CC organogel formulation.

Figure 10. Histological evaluation of blank group (A) and adjacent tissues injected with the formulation after 10 d (B). Original magnification: 400×.