Therapeutic efficacy of rifaximin loaded tamarind gum polysaccharide nanoparticles in TNBS induced IBD model Wistar rats

Abstract

Background: Rifaximin is a non-systemic antibiotic used in the treatment of inflammatory bowel disease (IBD). Antibiotics are demonstrating a significant role in the treatment of IBD by altering the dysbiotic colonic microbiota and decreases the immunogenic and inflammatory response in the patient population. Mucoadhesive colon targeted nanoparticles provide the site-specific delivery and extended stay in the colon. Since the bacteria occupy the lumen, spread over the surface of epithelial cells, and adhere to the mucosa, delivering the rifaximin as a nanoparticles with the mucoadhesive polymer enhances the therapeutic efficacy in IBD. The objective was to fabricate and characterize the rifaximin loaded tamarind gum nanoparticles and study the therapeutic efficacy in the TNBS-induced IBD model rats.

Materials and methods: The experimentation includes fabrication and characterization of drug excipient compatibility by FTIR. The fabricated nanoparticles were characterized for the hydrodynamic size and zeta potential by photon correlation spectroscopy and also analyzed by TEM. Selected best formulation was subjected to the therapeutic efficacy study in TNBS-induced IBD rats, and the macroscopic, microscopic and biochemical parameters were reported.

Results: The study demonstrated that the formulation TGN1 is best formulation in terms of nanoparticle characterization and hydrodynamic size which showed the hydrodynamic size of 171.4 nm and the zeta potential of -26.44 mV and other parameters such as TEM and drug release studies were also reported.

Conclusions: The therapeutic efficacy study revealed that TGN1 is efficiently reduced the IBD inflammatory conditions as compared to the TNBS control group and reference drug mesalamine group.

Keywords: IBD; nanoparticles; rifaximin; tamarind gum.

Figure 1

Overlay spectrum of Fourier transformed infrared (FTIR)

Figure 2

Optimization of hydrodynamic particles size (TGN1–TGN5)

Figure 3

Particle size analysis and zeta potential of selected best formulations (TGN1–TGN3). A. Hydrodynamic size distribution of TGN1. B. Hydrodynamic size distribution of TGN2. C. Hydrodynamic size distribution of TGN3. D. Zeta potential of TGN1

Figure 4

TEM images of TGN1 shows images in different magnification (A) TGN1 imaged at 30,000X magnification shows the uniformity of the nanoparticles in TEM imaging (B) TGN1 imaged at 60000X magnification (C) TGN1 imaged at 150000X, demonstrated the size of the nanoparticles in 19.0 nm, 32.6 nm and 29.1 nm (D) TGN1 imaged at 400000× and shows the individual TGP nanoparticles the contrast point inside the nanoparticles indicated the drug loading of rifaximin

Figure 5

Cumulative percentage of drug release of TGN1–TGN3

Figure 6

A. Animal body weight profile; B. Ulcer index; C. Colon profile. Values as expressed as Mean ± SEM; n = 5 animal/group value are expressed as mean ± SEM; n = 5 animals/group.*p < 0.05 significant different from TNBS colitis by one-way ANOVA

Figure 7

A. Haematological profile; B. Platelet profile. Values as expressed as mean ± SEM; n = 5 animal/group. Value are expressed as mean ± SEM; n = 5 animals/group. *p < 0.05 significant different from control group, #p < 0.05 significant different from TNBS colitis by one-way ANOVA

Figure 8

Biochemical analysis of colon lysate. A–C. Effect of TGN1 on (A), GSH (B), SOD (C), MDA in colon lysate of TNBS-induced Wistar rats; D. Effect of TGN1 on NO in colon lysate of TNBS-induced Wistar rats; E. Effect of TGN1 on TNFα in colon lysate of TNBS-induced Wistar rats; F. Effect of TGN1 in on MPO colon lysate of TNBS-induced Wistar rats. Value are expressed as mean ± SEM; n = 5 animals/group.*p < 0.05 significantly different from TNBS colitis by one-way ANOVA

Figure 9

Tamarind gum–rifaximin nanoparticles on histopathology of TNBS-induced IBD model of Wistar rats. A. Normal control; B. TNBS control; C. Mesalamine treated group; D. TGN1 treated group. IGL — intestinal glands; NMS — normal mucosa; MUS — muscularis mucosa; SM — submucosa; OD — oedema; CA — crypt abscess; CH — crypt hyperplasia; IL — infiltration of leucocytes