Self-assembling polymeric nanocarriers to target inflammatory lesions in ulcerative colitis

Courthion, Herve; Mugnier, Thibault; Rousseaux, Christel; Möller, Michael; Gurny, Robert; Gabriel, Doris

doi:10.1016/j.jconrel.2017.07.044

Cited by 30 publications

(17 citation statements)

References 33 publications

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“…Anti-inflammatory drugs such as cytokine antagonists and immunosuppressive drugs such as corticosteroids are currently used for IBD treatment [ 10 – 12 ]. However, long-term use of cytokine antagonists may have severe side effects [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

Zheng

et al. 2020

Mediators of Inflammation

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Inflammatory bowel disease, a gut disease that is prevalent worldwide, is characterized by chronic intestinal inflammation, such as colitis, and disorder of the gut microbiome. Glycine (Gly) is the simplest amino acid and functions as an anti-inflammatory immune-nutrient and intestinal microbiota regulator. This study aimed at investigating the effect of Gly on colitis induced in mice by intrarectal administration of 5% acetic acid (AA). Bodyweight and survival rates were monitored, and colonic length and weight, serum amino acid concentrations, intestinal inflammation-related gene expression, and colonic microbiota abundances were analyzed. The results showed that Gly dietary supplementation had no effect on the survival rate or the ratio of colonic length to weight. However, Gly supplementation reversed the AA-induced increase in serum concentrations of amino acids such as glutamate, leucine, isoleucine, and valine. Furthermore, Gly inhibited colonic gene expression of interleukin- (IL-) 1β and promoted IL-10 expression in colitis mice. Gly supplementation also reversed the AA-induced reduction in the abundance of bacteria such as Clostridia, Ruminococcaceae, and Clostridiales. This change in the intestinal microbiota was possibly attributable to the changes in colonic IL-10 expression and serum concentrations of valine and leucine. In sum, Gly supplementation regulated the serum concentrations of amino acids, the levels of colonic immune-associated gene expression, and the intestinal microbiota in a mouse model of colitis. These findings enhance our understanding of the role of Gly in regulating metabolism, intestinal immunity, and the gut microbiota in animals afflicted with colitis.

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Section: Introductionmentioning

confidence: 99%

The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

Zheng

et al. 2020

Mediators of Inflammation

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“…In another study in mice, superior alleviation of trinitrobenzene-sulfonic acid (TNBS)-induced colitis by intrarectal administration of CSA-loaded NPs was reported. 19 However, rectal administration is not easily managed by patients and the most desired and accepted way to administer the drug in UC therapy is orally. CSA-loaded poly(lactic-co-glycolic acid) (PLGA) NPs and microparticles have been evaluated for the treatment of DSS-induced colitis in mice and their efficacy has been compared with that of Neoral.…”

Section: Introductionmentioning

confidence: 99%

Colon-targeted delivery of cyclosporine A using dual-functional Eudragit<sup>®</sup> FS30D/PLGA nanoparticles ameliorates murine experimental colitis

Naeem¹,

Bae²,

Oshi³

et al. 2018

IJN

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BackgroundColon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer.MethodsCSA-loaded Eudragit FS30D nanoparticles (ENPs), PLGA nanoparticles (PNPs), and Eudragit FS30D/PLGA nanoparticles (E/PNPs) were prepared using the oil-in-water emulsion method. Scanning electron microscope images and zeta size data showed successful preparation of CSA-loaded NPs.ResultsPNPs exhibited a burst drug release of >60% at pH 1.2 (stomach pH) in 0.5 h, which can lead to unwanted systemic absorption and side effects. ENPs effectively inhibited the burst drug release at pH 1.2 and 6.8 (proximal small intestine pH); however, nearly 100% of the CSA in ENPs was released rapidly at pH 7.4 (ileum–colon pH) owing to complete NP dissolution. In contrast to single-functional PNPs and ENPs, the dual-functional E/PNPs minimized burst drug release (only 18%) at pH 1.2 and 6.8, and generated a sustained release at pH 7.4 thereafter. Importantly, in distribution studies in the gastrointestinal tracts of mice, E/PNPs significantly improved CSA distribution to the colon compared with PNPs or ENPs. In a mouse model of colitis, E/PNP treatment improved weight loss and colon length, and decreased rectal bleeding, spleen weight, histological scoring, myeloperoxidase activity, macrophage infiltration, and expression of proinflammatory cytokines compared with PNPs or ENPs.ConclusionOverall, this work confirms the benefits of CSA-loaded E/PNPs for efficiently delivering CSA to the colon, suggesting their potential for UC therapy.

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“…Research related to the negatively charged surface design of nanoparticles for accurate therapy of the inflamed colon has become a research hotspot. PEGylation with neutral to slightly negative net charge is a common surface modification, 44,60 and the surface coating of negatively charged heparin (HEP), hyaluronic acid (HA), 61,62 and nanozymes 63 can also increase the accumulation of nanoparticles with positively charged proteins on the inflamed mucosa. 64 For instance, nanozyme-based nanoparticles with a negative surface charge showed enhanced passive targeting and inflammation relief.…”

Section: Passive Targetingmentioning

confidence: 99%

Recent Progress in the Diagnosis and Precise Nanocarrier-Mediated Therapy of Inflammatory Bowel Disease

Wang¹,

Yu²,

Yang³

2021

JIR

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The effective colon drug delivery remains to be an international frontier research in inflammatory bowel disease (IBD) therapy. The exploration and research of nanocarrier-based nanomedicine with great potential brings new opportunities for IBD therapy and diagnoses. Functional nanocarriers with varying morphology and characteristics can not only effectively avoid the destruction of the complex gastrointestinal (GI) tract microenvironment but also endow drugs with target therapy and improved bioavailability, thus elevating therapeutic efﬁcacy. In this review, we illustrated several challenges in IBD therapy, then emphasis on some latest research progress of nanoparticles based therapy of oral administration, rectal administration and parenteral administration, as well as IBD diagnoses. Finally, we described the future perspective of nanocarriers in the treatment and diagnoses of IBD.

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Self-assembling polymeric nanocarriers to target inflammatory lesions in ulcerative colitis

Cited by 30 publications

References 33 publications

The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

Colon-targeted delivery of cyclosporine A using dual-functional Eudragit<sup>®</sup> FS30D/PLGA nanoparticles ameliorates murine experimental colitis

Recent Progress in the Diagnosis and Precise Nanocarrier-Mediated Therapy of Inflammatory Bowel Disease

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Self-assembling polymeric nanocarriers to target inflammatory lesions in ulcerative colitis

Cited by 30 publications

References 33 publications

The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

Colon-targeted delivery of cyclosporine A using dual-functional Eudragit<sup>&reg;</sup>&nbsp;FS30D/PLGA&nbsp;nanoparticles ameliorates murine experimental colitis

Recent Progress in the Diagnosis and Precise Nanocarrier-Mediated Therapy of Inflammatory Bowel Disease

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Colon-targeted delivery of cyclosporine A using dual-functional Eudragit<sup>®</sup> FS30D/PLGA nanoparticles ameliorates murine experimental colitis