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Research Article

Nanoparticle-based delivery enhances anti-inflammatory effect of low molecular weight heparin in experimental ulcerative colitis

, , , , , & show all
Pages 811-817 | Received 20 Mar 2017, Accepted 25 Apr 2017, Published online: 16 May 2017

Figures & data

Figure 1. Scanning electron microscope images (SEM) of the blank PEMT NP.

Figure 1. Scanning electron microscope images (SEM) of the blank PEMT NP.

Figure 2. CLSM images showing macrophages with stained nuclei after 2 h incubation with fluorescein labeled LMWH or LMWH-NP.

Figure 2. CLSM images showing macrophages with stained nuclei after 2 h incubation with fluorescein labeled LMWH or LMWH-NP.

Figure 3. Release of TNF-α and IL-6 from LPS-stimulated macrophages after 8 h of incubation with LMWH (1 IU/ml) and LMWH-NP (0.1 mg/ml). n = 3, data represent mean SD. * = p < 0.05 compared to stimulated cells.

Figure 3. Release of TNF-α and IL-6 from LPS-stimulated macrophages after 8 h of incubation with LMWH (1 IU/ml) and LMWH-NP (0.1 mg/ml). n = 3, data represent mean SD. * = p < 0.05 compared to stimulated cells.

Figure 4. Clinical activity score (CAS) of mice. After colitis induction, the animals were treated for 3 days with rectal injection of blank and LMWH-loaded NP. The drug and LMWH-NP dose were equal to 100 IU/kg (left), or 500 IU/kg (Right). The free drug showed no significant improvement while treatment with LMWH-NP (500 IU/kg) has significantly improved the CAS of colitis mice. n = 5, * = p < 0.05 compared with colitis control group given saline. $=p < 0.05 compared with colitis groups given LMWH (500 IU/kg).

Figure 4. Clinical activity score (CAS) of mice. After colitis induction, the animals were treated for 3 days with rectal injection of blank and LMWH-loaded NP. The drug and LMWH-NP dose were equal to 100 IU/kg (left), or 500 IU/kg (Right). The free drug showed no significant improvement while treatment with LMWH-NP (500 IU/kg) has significantly improved the CAS of colitis mice. n = 5, * = p < 0.05 compared with colitis control group given saline. $=p < 0.05 compared with colitis groups given LMWH (500 IU/kg).

Figure 5. Colon tissues of mice treated with LMWH and LMWH-NP formulations. The dose of both the drug and drug-loaded NP was equal to 500 IU/kg. Neither clear necrosis in the crypt nor an obvious damage was detected in the colonic mucosa of LMWH-NP groups, while clear necrosis was observed in the disrupted colon architecture in the other groups.

Figure 5. Colon tissues of mice treated with LMWH and LMWH-NP formulations. The dose of both the drug and drug-loaded NP was equal to 500 IU/kg. Neither clear necrosis in the crypt nor an obvious damage was detected in the colonic mucosa of LMWH-NP groups, while clear necrosis was observed in the disrupted colon architecture in the other groups.

Figure 6. Levels of the inflammatory cytokines in the colon tissue of colitis mice after treatment with LMWH, blank NP and LMWH-NP. Data are shown as mean ± S.D (n = 5). *, $= p < 0.05 compared to each of the colitis control and LMWH groups respectively. Only LMWH-NP (500 IU/kg) were able to achieve an efficient and significant reduction of TNF-α IL-1β in comparison with colitis control, while LMWH (100 IU/kg) showed no significant efficiency. Both the blank and drug-loaded NP have significantly reduced the levels of IL-6.

Figure 6. Levels of the inflammatory cytokines in the colon tissue of colitis mice after treatment with LMWH, blank NP and LMWH-NP. Data are shown as mean ± S.D (n = 5). *, $= p < 0.05 compared to each of the colitis control and LMWH groups respectively. Only LMWH-NP (500 IU/kg) were able to achieve an efficient and significant reduction of TNF-α IL-1β in comparison with colitis control, while LMWH (100 IU/kg) showed no significant efficiency. Both the blank and drug-loaded NP have significantly reduced the levels of IL-6.
Supplemental material

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