Assessment of the drug loading, in vitro and in vivo release behavior of novel pH-sensitive hydrogel

Figures & data

Scheme 1. Synthesis scheme of pH-sensitive P(LE-IA-MEG) hydrogel. (A) synthesis of MPEG-PLA copolymer; (B) synthesis of PLE-AC copolymer; and (C) synthesis of P(LE-IA-MEG) hydrogel.

Table 1. Dexamethasone solution prepared by ethanol, 1,2-propanediol and ethanol–water mixed solution, respectively.

Solution	Concentration	Preparation method
a	2.5 mg/ml DEX ethanol solution	5 mg DEX + 2 ml ethanol
b	2.5 mg/ml 1,2-propanediol DEX solution	5 mg DEX + 2 ml 1,2-propanediol
c	12.5 mg/ml DEX ethanol solution	5 mg DEX + 400 µl ethanol + 1600 µl deionized water

Figure 1. X-ray powder diffraction pattern of (a) blank hydrogel; (b) dexamethasone; and (c) dexamethasone hydrogel.

Figure 2. DSC curves of (a) blank hydrogel; (b) dexamethasone hydrogel; and (c) dexamethasone. Heating and cooling rate were 10 °C/min.

Figure 3. In vitro release behavior of dexamethasone from dexamethasone P(LE-IA-MEG) hydrogel samples prepared by 1,2-propanediol, ethanol-water mixed solution and ethanol, respectively. At pH 1.2 (from 0 to 2 h), pH 6.8 (from 3 to 6 h) and pH 7.4 (from 7 to 10 h).

Figure 4. Schematic illustration of the swelling condition of dexamethasone hydrogel in dissolution medium of different pH values (a) pH 1.2 artificial gastric juice at 2 h, (b) pH 6.8 artificial small intestinal juice at 4 h, (c) pH 7.4 artificial colonic juice at 10 h; the dexamethasone hydrogels were prepared in ethanol, 1,2-propanediol and the ethanol–water mixed solution from left to right).

Figure 5. In vitro release behavior of dexamethasone from dexamethasone P(LE-IA-MEG) hydrogel samples prepared in four kinds of ethanol–water mixed solution in different ratios, respectively. At pH 1.2 (from 0 to 2 h), pH 6.8 (from 3 to 6 h) and pH 7.4 (from 7 to 10 h).

Table 2. Four kinds of ethanol–deionized water mixed solution of dexamethasone.

Sample	Concentration of DEX ethanol solution (mg/ml)	Volume of DEX ethanol solution (ml)	Volume of water (ml)
S-1	12.5	0.4	1.6
S-2	6.25	0.8	1.2
S-3	5	1.0	1.0
S-4	3.125	1.6	0.4

Table 3. Recovery and precision for dexamethasone determination in rats' plasma by HPLC.

Concentration (µg/ml)	Recovery (%)	RSD within-day (%)	RSD between-day (%)
0.5	90.75 ± 5.5	9.4	8.6
5	85.26 ± 7.8	5.8	6.0
20	85.98 ± 4.9	5.7	6.3

Figure 6. Plasma concentration curves of dexamethasone (i.g. administration of 5 µmol/kg) and dexamethasone hydrogel (i.g. administration of hydrogel containing 5μmol/kg dexamethasone) in rats (data are mean ± SD, n = 6).

Table 4. Pharmacokinetic parameter of free dexamethasone and dexamethasone hydrogel in rats' blood after i.g. administration of dexamethasone (5 µmol/kg) and dexamethasone hydrogel containing 5 µmol/kg dexamethasone (data are mean ± SD, n = 6).

Parameter	Free DEX	DEX-hydrogel
Tmax/h	1.0 ± 0.08	3.9 ± 0.47
Cmax/µg/ml	2.16 ± 0.09	0.43 ± 0.02
AUC0–12/µg h/ml	8.29 ± 0.59	3.70 ± 0.17
AUC0-∞/µg h/ml	8.97 ± 0.23	4.44 ± 0.15
MRT0–12/h	3.27 ± 0.07	5.49 ± 0.13
MRT0–∞/h	3.68 ± 0.62	7.47 ± 0.21

Scheme 2. Schematic swelling behavior and drug diffusional illustration of dexamethasone P(CE-MAA-MEG) hydrogel with different solution media at pH 1.2 and 6.8/7.4, respectively.

Scheme 3. Schematic preparation, administration and in vivo transportation of pH-sensitive dexamethasone P(CE-MAA-MEG) hydrogel.