Determination of the mitigating effect of colon-specific bioreversible codrugs of mycophenolic acid and aminosugars in an experimental colitis model in Wistar rats

Table 1 Doses of test and standard compounds

Groups	Dose1 (mg/kg)
HC	0.9% saline (1 mL)
MPA	18.5
MMF	25.0
MGLS	28.5
MGAS	28.5
D- Glucosamine	12.4
D- Galactosamine	12.4
MPA + GL	18.5 + 12.4
MPA + GA	18.5 + 12.4

¹All doses were calculated on an equimolar basis to the dose of MPA. HC: Healthy control; MPA: Mycophenolic acid; MMF: Mycophenolate mofetil; MGLS: Prodrug of MPA and D-glucosamine; MGAS: Prodrug of MPA and D-galactosamine; MPA + GL: Physical mixture of MPA and D-glucosamine; MPA + GA: Physical mixture of MPA and D-galactosamine.

Table 2 Results of in vitro release in different incubation media

Prodrug	Incubation media
	Aqueous buffers pH 1.2 and pH 7.4	Stomach and intestinal homogenates	Colon homogenate				Faecal matter
			K ± SD (min-1)1	t1/2 (min)	% Prodrug hydrolysed	% MPA released	% Prodrug hydrolysed	% MPA released
MGLS	Stable	1.30%	0.0025 ± 0.000978	275	92.6	86.7	63	54
MGAS	Stable	14-19%	0.000108 ± 0.00001	305	79.15	76.4	47	52

¹Average of six readings, follows first-order kinetics. MGLS: Prodrug of mycophenolic acid and D-glucosamine; MGAS: Prodrug of mycophenolic acid and D-galactosamine.

Table 3 Disease activity score rate

Groups	Days
	1	2	3	4	5	6	7	8	9	10	11
HC	0	0	0	0	0	0	0	0	0	0	0
DC	0	0.67 ± 1.15	0.87 ± 1.50	2.53 ± 0.50	2.63 ± 0.65	2.63 ± 0.65	2.97 ± 0.85	3.12 ± 1.80	3.22 ± 1.70	3.23 ± 2.00	3.30 ± 2.0
MMF	0	0.33 ± 0.58	0.67 ± 1.15	1.07 ± 1.29	1.53 ± 0.50	2.53 ± 0.0	2.10 ± 0.85	1.07 ± 0.51	0.73 ± 0.81	0.23 ± 0.68	0c
MPA	0	0.43 ± 0.75	0.67 ± 1.15	2.50 ± 0.17	2.63 ± 0.35	2.63 ± 0.35	2.33 ± 0.58	1.97 ± 0.65	1.63 ± 0.91	0.97 ± 0.85	0.77 ± 0.68c
MGLS	0	0.33 ± 0.58	0.33 ± 0.58	1.77 ± 0.40	1.97 ± 0.65	2.53 ± 1.08	1.73 ± 1.03	1.06 ± 0.50	0.63 ± 0.65	0.33 ± 0.17	0c
MGAS	0	0.33 ± 0.58	0.43 ± 0.75	1.53 ± 0.81	2.10 ± 0.17	2.33 ± 0.58	1.73 ± 1.03	0.93 ± 0.58	0.73 ± 0.81	0.50 ± 0.35	0.30 ± 0.1c
GL	0	0.33 ± 0.58	0.67 ± 1.15	2.1 ± 0.85	2.3 ± 0.89	2.53 ± 0.50	2.1 ± 0.85	1.73 ± 0.75	1.40 ± 0.17	1.20 ± 0.40	1.02 ± 0.2b
GA	0	0.43 ± 0.75	0.67 ± 1.15	2.17 ± 0.75	2.53 ± 0.50	2.53 ± 0.52	2.33 ± 0.58	2.10 ± 0.85	1.50 ± 1.01	1.39 ± 1.00	1.30 ± 0.4b
GL + MPA	0	0.33 ± 0.58	0.33 ± 0.58	1.83 ± 0.68	2.17 ± 0.75	2.17 ± 0.75	1.87 ± 0.51	1.30 ± 0.70	0.93 ± 0.58	0.53 ± 0.50	0.40 ± 0.35c
GA + MPA	0	0.33 ± 0.58	0.667 ± 1.15	1.97 ± 0.65	1.97 ± 0.654	2.3 ± 0.89	1.77 ± 0.51	1.17 ± 0.51	0.73 ± 0.23	0.53 ± 0.50	0.40 ± 0.35c

Average of six readings; two-way ANOVA followed by Bonferroni’s Test, statistical significance considered at

^cP < 0.001 Disease control. HC: Healthy control; DC: Disease control; MMF: Mycophenolate mofetil; MPA: Mycophenolic acid; MGLS: Prodrug of MPA and D-glucosamine; MGAS: Prodrug of MPA and D-galactosamine; GL: D-glucosamine; GA: D-galactosamine; GL+MPA: Physical mixture of D-glucosamine and MPA; GA + MPA oral: Physical mixture of D-galactosamine and MPA.