Investigation of the colon-targeting, improvement on the side-effects and therapy on the experimental colitis in mouse of a resin microcapsule loading dexamethasone sodium phosphate

Figures & data

Table 1. The scoring system of disease activity index (DAI) of mouse.

Weight loss	Excrement character	Fecal occult blood	Score
<0%	Normal	Normal	0
1–5%	Friable	Occult blood+	1
5–10%		Occult blood++	2
10–15%	Diarrhea	Occult blood+++	3
>15%		Visible blood in the stool	4

Table 2. The assay criteria of O-benzidine to determine the fecal occult blood of mouse.

Results	Phenomenon
Normal	No color occurred after adding reagents for 2 min
Occult blood+	Light blue occurred at first, then turn blue after adding reagents for 10 s
Occult blood++	Light blue occurred at first, then turn brown after adding reagents
Occult blood+++	Brown occurred immediately after adding reagents

Figure 1. The variation of the drug-loading capacity (Q) of resin versus time during the DXSP-IER preparation.

Figure 2. The in vitro release behavior of (A) DXSP-IER in the physiological saline (PS) and (B) DXSP-DRM. The in vitro release experiment of DXSP-DRM was successively conducted 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), respectively.

Table 3. Recovery and precision for DXSP determination in rat plasma by HPLC.

Concentration (g/ml)	Recovery (%)	RSD within-day (%)	RSD between-day (%)
0.15	103.6 ± 8.4	4.79	4.33
5	95.7 ± 9.1	4.21	3.79
40	100.2 ± 3.7	2.12	1.99

Figure 3. The plasma concentration–time curves in rats of DXSP solution (p.o. administration of 5 mg/kg) and DXSP-DRM solution (p.o. administration of hydrogel containing 5 mg/kg dexamethasone; data are mean ± SD, n = 6).

Table 4. Pharmacokinetic parameters of DXSP and DXSP-DRM in rat plasma after p.o. administration of DXSP solution (5 mg/kg) and DXSP-DRM containing 5 mg/kg DXSP (data are mean ± SD, n = 6).

Parameters	DXSP	DXSP-DRM
Tmax (h)	0.69 ± 0.03	2.25 ± 0.02**
Cmax (μg/ml)	6.98 ± 0.33	4.08 ± 0.21**
AUC0–12 (μg h/ml)	16.51 ± 1.89	6.79 ± 1.51**

Compared with the DXSP group: **p < 0.01.

Figure 4. The distribution of DXSP in the gastrointestinal contents at different times after orally administered with DXSP-DRM solution (data are mean ± SD, n = 15).

Figure 5. The influence of DXSP and DXSP-DRM on the body weight changes (A) and the ultimate body weight after 10 days (B) of mouse in the improvement of DXSP-DRM on the adverse reaction induced by DXSP (data are mean ± SD, n = 12). #,*Mean values with different superscript symbols were significantly different. ##p < 0.01, #p < 0.05 compared to the control group; *p < 0.05 compared to the TNBS group. Control, control group; DXSP, DXSP p.o. group; DXSP-DRM, DXSP-DRM p.o. group.

Figure 6. The influence of DXSP and DXSP-DRM on the spleen index (A) and the thymus index (B) of mouse (data are mean ± SD, n = 12). #,*Mean values with different superscript symbols were significantly different. ##p < 0.01, #p < 0.05 compared to control group; *p < 0.05 compared to TNBS group. Control, control group; DXSP, DXSP p.o. group; DXSP-DRM, DXSP-DRM p.o. group.

Figure 7. (A) The influence of DXSP and DXSP-DRM on the survival rate of mouse. (B) The influence of DXSP and DXSP-DRM on the body weight changes of mouse (data are shown as mean ± SD, n = 15). Control, control group; TNBS, TNBS group; DXSP, DXSP p.o. group; DXSP-DRM, DXSP-DRM p.o. group.

Figure 8. The influence of DXSP and DXSP-DRM on the variation of DAI index (A) and the ultimate DAI index after 5 days (B) of mouse (data are mean ± SD, n = 15). ##,**Mean values with different superscript symbols were significantly different. ##p < 0.01, compared to control group; **p < 0.01 compared to TNBS group. Control, control group; TNBS, TNBS group; DXSP, DXSP p.o. group; DXSP-DRM, DXSP-DRM p.o. group.

Figure 9. The influence of DXSP and DXSP-DRM on the activity of MPO in the colonic tissue of mouse. ##,**Mean values with different superscript symbols were significantly different. ##p < 0.01 compared to control group; **p < 0.01 compared to TNBS group. Control, control group; TNBS, TNBS group; DXSP, DXSP p.o. group; DXSP-DRM, DXSP-DRM p.o. group.

Scheme 1. Schematic preparation, administration and in vivo transportation of DXSP-DRM.