Evaluation of in vivo efficacy and toxicity of prednisolone-loaded hydrogel-based drug delivery device

Abstract

Drugs prescribed for the treatment of moderate to severe inflammatory bowel disease (IBD) are associated with number of side effects. Targeted drug delivery is essential for the treatment of inflammatory bowel disease in order to increase efficacy and reduce toxicity. The established delivery system is designed on enzyme and time-based release of poorly soluble prednisolone, a drug of choice for the treatment of moderate to severe inflammatory bowel disease. Their pharmacological evaluation was done in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced model of colitis in rat. The drug was administered once daily for 3 consecutive days. Visible severity of colitis, tissue to bodyweight ratio, tissue histology along with nitric oxide (NO), malondialdehyde (MDA) and myeloperoxidase (MPO) activity of colonic tissue were studied to estimate the efficacy of the drug-loaded delivery system. The highest efficacy was observed for formulation in which Eudragit RS100 (EU) was used along with guar gum (GG) in a ratio 2:5 for the preparation of delivery device. An effective recovery was observed from the study of tissue histology of animals treated with the drug-loaded optimized formulation and the biochemical parameters supported it. The toxicity of prednisolone (PD) was reduced significantly as predicted from thymus to body weight ratio of treated animals. GG and EU RS100 provided a newer bipolymer combination for the colon-targeted delivery of PD which increased its efficacy and reduced the toxic side effects. The in vivo experiments presented effective amelioration from colitis in TNBS-induced animal model of colitis.

Keywords: Colon; TNBS colitis; eudragit RS100; guar gum; prednisolone.

Figure 1

Schedule for the development of colitis model and subsequent treatment with healing drug

Figure 2

Cumulative drug release studies in simulated colonic fluid for formulations T1 to T9

Figure 3

FTIR spectrum of prednisolone (a) guar gum (b) Eudragit RS100 (c) polymer combination (d) and formulation T9 (e)

Figure 4

XRD spectrum of prednisolone (a), GG (b), Eudragit (c), polymer combination (d), formulation T9 (e)

Figure 5

AFM images of formulation T1 (a), T9 (b), and Guar gum (c)

Figure 6

Representative longitudinal sectional view of colon of healthy rat (a), 2,4,6-trinitrobenzene sulphonic acid control (b), prednisolone (c), prednisolone loaded in guar gum matrix (d), and prednisolone loaded in guar gum-eudragit RS100 bipolymer matrix (e) group of rats

Figure 7

Representative histological appearance of rat colon: Normal colon of healthy rats at 10× magnification (a) and 40× magnification (b), Colon of 2,4,6-trinitrobenzene sulphonic acid-induced colitis group at 10× magnification (c), and 40× magnification (d), prednisolone treated colon of rats at 10× magnification (e), and at 40× magnification (f), prednisolone loaded in guar gum matrix-treated colon of rats at 10× magnification (g) and at 40× magnification (h), prednisolone loaded in guar gum-eudragit RS100 bipolymer matrix-treated colon of rats at 10× magnification (i), and at 40× magnification (j)

Figure 8

Plasma concentration-time graph of prednisolone after oral administration of prednisolone in delivery system and prednisolone alone. The data are represented as the mean ± standard deviation (n=3)