Preparation and evaluation of conjugate nanogels of glycyl-prednisolone with natural anionic polysaccharides as anti-arthritic delivery systems

Figures & data

Figure 1. Synthesis of AL-GP and HA-GP.

Figure 2. Schematic diagram of nanogel formation by organic solvent evaporation.

Figure 3. In vivo experimental schedules for examination of efficacy of conjugate nanogels.

Figure 4. Size distributions of conjugate nanogels.

Table 1. Preparation of conjugate nanogels and their particle features.

Nanogel	AL-Na (mg)	HA (mg)	GP (mg)	WSC (mg)	NHS (mg)	PD content (%, w/w)	Particle size^a (nm)	Zeta potential^a (mV)
AL-GP-NG	60	–	30	500	300	3.4	444 ± 88	–24.9 ± 0.6
HA-GP-NG	–	60	30	500	300	5.6	304 ± 63	–19.3 ± 0.6

^a The results are expressed as the mean ± S.D. (n = 3).

Figure 5. In vitro release of PD from conjugate nanogels at pH 6 and 7.4 at 37 °C. The results are expressed as the mean ± S.D. (n = 3).

Figure 6. Plasma concentration–time profiles of free and total (free + conjugated) PD after i.v. administration of conjugate nanoparticles in normal rat. The results are expressed as the mean ± S.E. (n = 3).

Table 2. Pharmacokinetic parameters of free and total PD in i.v. administration of AL-GP-NG to rats.

Preparation	Species	Cmax (µg/mL)	Tmax (h)	AUC (0–7 h) (µg·h/mL)	MRT(0–7 h) (h)	VRT (0–7 h) (h^2)
PD alone	Free PD	1.61 ± 0.30	0.0 ± 0.0	1.91 ± 0.08	0.87 ± 0.05	0.67 ± 0.08
AL-GP-NG	Free PD	1.64 ± 0.03	0.5 ± 0.0	4.16 ± 0.01	2.41 ± 0.03**	4.22 ± 0.18**
	Total PD	41.84 ± 4.45**^,##	0.0 ± 0.0	144.69 ± 4.97**^,##	2.72 ± 0.04**^,##	5.06 ± 0.06**^,##

The results are expressed as the mean ± S.E. (n = 3).

** p< .01 vs. free PD (PD alone).

## p< .01 vs. free PD (AL-GP-NG).

Table 3. Pharmacokinetic parameters of free and total PD in i.v. administration of HA-GP-NG to rats.

Preparation	Species	Cmax (µg/mL)	Tmax (h)	AUC (0–7 h) (µg·h/mL)	MRT (0–7 h) (h)	VRT (0–7 h) (h^2)
PD alone	Free PD	1.61 ± 0.30	0.0 ± 0.0	1.91 ± 0.08	0.87 ± 0.05	0.67 ± 0.08
HA-GP-NG	Free PD	1.05 ± 0.10	0.5 ± 0.0	1.61 ± 0.18	1.37 ± 0.16*	0.97 ± 0.18
	Total PD	24.03 ± 3.08**^,##	0.0 ± 0.0	36.77 ± 3.91**^,##	1.38 ± 0.08*	1.86 ± 0.08**^,##

The results are expressed as the mean ± S.E. (n = 3).

* p< .05 vs. free PD (PD alone).

** p< .01 vs. free PD (PD alone).

## p< .01 vs. free PD (HA-GP-NG).

Figure 7. Change in body weight after i.v. administration of conjugate nanoparticles in rats with adjuvant-induced arthritis. The results are expressed as the mean ± S.E. (n = 3). *p< .05 vs. control.

Figure 8. Change in body weight after i.v. administration of conjugate nanoparticles in rats with adjuvant-induced arthritis. The results are expressed as the mean ± S.E. (n = 3). *p< .05 vs. control and ^#p< .05 vs. PD alone.