Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

Celasco, G.; Moro, Luigi; Bozzella, Roberta; Mangano, Katia; Quattrocchi, Cinzia; Aiello, Caterina; Donia, Marco; Fagone, Paolo; Marco, Roberto Di

doi:10.1007/s10620-008-0344-5

Cited by 6 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent experimental data proved that parnaparin sodium, a LMWH with a mean molecular mass around 5000, delivered by catheter into the colon of rat was highly effective in ameliorating dinitrobenzene (DNB)-induced colitis [53] . This lead to the suggestion that the administration of parnaparin sodium, contained in tablets delivering the product directly into the lumen of the colon, could represent a promising approach to treat UC.…”

Section: Parnaparin MMXmentioning

confidence: 99%

Recent advances in the management of distal ulcerative colitis

Koutroubakis¹

2010

WJGPT

View full text Add to dashboard Cite

The most frequent localization of ulcerative colitis (UC) is the distal colon. In treating patients with active distal UC, efficacy and targeting of the drug to the distal colon are key priorities. Oral and rectal 5-aminosalicylic acid (5-ASA) preparations represent the first line therapy of mild-to-moderate distal UC for both induction and maintenance treatment. It has been reported that many UC patients are not adherent to therapy and that noncompliant patients had a 5-fold risk of experiencing a relapse. These findings led to the introduction of oncedaily oral regimens of 5-ASA as better therapeutic options in clinical practice due to improved adherence. New formulations of mesalazine, including the multimatrix delivery system, and mesalazine granules, which allow once-daily administration, have been developed. They have been demonstrated to be efficacious in inducing and maintaining remission in mild-to-moderate distal UC in large clinical trials. However, existing data for distal UC are rather insufficient to make a comparison between new and classical 5-ASA formulations. It seems that the new formulations are at least as effective as classical oral 5-ASA formulations. Other treatment options, in the case that 5-ASA therapy is not effective, include systemic corticosteroids, thiopurines (azathioprine or 6-mercaptopurine), cyclosporine, infliximab and surgery. The combination of a prompt diagnostic workup, a correct therapeutic approach and an appropriate follow-up schedule is important in the management of patients with distal UC. This approach can shorten the duration of symptoms, induce a prolonged remission, improve patient's quality of life, and optimize the use of health resources.

show abstract

Section: Parnaparin MMXmentioning

confidence: 99%

Recent advances in the management of distal ulcerative colitis

Koutroubakis¹

2010

WJGPT

View full text Add to dashboard Cite

show abstract

“…A role for accelerated thrombin production in IBD is also supported by reports describing significantly reduced antithrombin III (ATIII) levels in plasma of patients with IBD (9,22). Clinical studies have yielded conflicting results on the therapeutic efficacy of heparin in patients with IBD (4,22), although the antithrombin agent has shown some benefit in blunting the inflammation and tissue injury in experimental colitis (3,25). Although the beneficial effects of heparin in human and experimental IBD have been attributed to its anti-inflammatory properties (22), the efficacy of heparin and other antithrombin agents in preventing the thrombus formation associated with IBD has not been previously addressed.…”

mentioning

confidence: 99%

Thrombin mediates the extraintestinal thrombosis associated with experimental colitis

Yoshida

Russell

Granger³

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…A major advantage of oral or rectal administration of heparins is the subsequent local effect combined with minimal systemic availability essentially providing a therapeutic approach without adverse effects (Pellequer et al, 2007). However, all precedent studies were based on systems with limited specificity in delivery (Pellequer et al, 2007;Celasco et al, 2008;Lean, et al, 2015b). NP in the size range of about 100 nm have proven a high potential of adherence to inflamed colon tissues (Lamprecht et al, 2001); therefore, such NP are most suitable in combination with LMWH to achieve a maximum benefit for UC therapy.…”

Section: Discussionmentioning

confidence: 99%

“…However, due to its hemorrhagic adverse effects after systemic availability, a broad clinical use in IBD therapy was impossible. First attempts by epithelial delivery of LMWH elucidated the potential of this therapeutic approach benefitting of low systemic bioavailability and subsequent minimal adverse effect levels (Pellequer et al, 2007;Celasco et al, 2008;Luo et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2017

View full text Add to dashboard Cite

Epithelial administration of low molecular weight heparin (LMWH) has proven its therapeutic efficiency in ulcerative colitis (UC) but still lacks of a sufficiently selective drug delivery system. Polymeric nanoparticles were used here not only to protect LMWH from intestinal degradation but also to provide targeted delivery to inflamed tissue in experimental colitis mice. LMWH was associated with polymethacrylate nanoparticles (NP) type A (PEMT-A) or type B (PEMT-B) of a size: 150 nm resulting in a maximum drug loading: 0.1 mg/mg. In a lipopolysaccharidestimulated macrophages both, free LMWH and LMWH-NP have significantly reduced the cytokines secretion independently from cellular uptake. The in-vivo therapeutic efficiency was dose dependent as at low doses (100 IU/kg) only minor differences between free LMWH and LMWH-NP were found and the superiority of LMWH-NP became prominent with dose increase (500 IU/kg). Administration of LMWH-NP at 500 IU/kg has markedly improved the clinical activity as compared to LMWH while similarly pathophysiological indicators revealed increased therapeutic outcome in presence of NP compared to LMWH alone: Myeloperoxidase (Colitis control: 10 480 ± 5335, LMWH-PEMT-A NP: 1507 ± 2165, LMWH-PEMT-B NP: 382 ± 143, LMWH: 8549 ± 5021 units/g) and tumor necrosis factor: (Colitis control: 1636 ± 544, LMWH-PEMT-A NP: 511 ± 506, LMWH-PEMT-B NP: 435 ± 473, LMWH: 1110 ± 309 pg/g). Associating LMWH with NP is improving the anti-inflammatory efficiency of LMWH in-vivo by its protection against degradation in luminal environment and selective drug delivery. Such a combination holds promise for a highly specific therapy by its double selectivity towards the inflamed intestinal tissue. LMWH-PEMT NP have significantly improved the clinical activity in-vivo in comparison to free LMWH.

show abstract

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

Abstract: The following error was published in Table 2 of this article. LMWH-A, LMWH-C, and UFH are not properly aligned. This makes it impossible to link the drugs to the correct doses and to the effects, and so the information is greatly misleading. The correct Table 2 appears below.

Cited by 6 publications

References 0 publications

Recent advances in the management of distal ulcerative colitis

Recent advances in the management of distal ulcerative colitis

Thrombin mediates the extraintestinal thrombosis associated with experimental colitis

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

Contact Info

Product

Resources

About