New targeting strategies in drug therapy of inflammatory bowel disease: mechanistic approaches and opportunities

Wolk, Omri; Epstein, Svetlana; Ioffe-Dahan, Viktoriya; Ben‐Shabat, Shimon; Dahan, Arik

doi:10.1517/17425247.2013.800480

Cited by 23 publications

(15 citation statements)

References 132 publications

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“…Colon-specific drug delivery systems thwart drug release in physiological milieu of the stomach and small intestine, and endow an onset of drug release in colon [40]. In this context, various approaches have been designed and developed to achieve the desired goals including timed release systems, pressure controlled systems, osmotically controlled systems, pH sensitive polymer coating, pro-drugs and bioresponsive microspheres [41]. Among these, pH dependent and colonic microflora responsive drug delivery systems revealed potential validated results that proved in clinical translation [42,43].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore majority of the clinical trials (79%) have been conducted for triggered release systems (pH dependent and microflora assisted). The presence of microflora and polysaccharidase enzyme mediated biochemical activities in the ascending colon represents an exclusive and non-continuous event independent of GI transit time and pH [41,43]. Hence, microflora triggered drug delivery systems tendering greater degree of mucoadhesiveness would be highly advantageous for the treatment of colitis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Wheat germ agglutinin anchored chitosan microspheres of reduced brominated derivative of noscapine ameliorated acute inflammation in experimental colitis

Kaur

Sodhi

Katyal

et al. 2015

Colloids and Surfaces B: Biointerfaces

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Wheat germ agglutinin anchored chitosan microspheres of reduced brominated derivative of noscapine ameliorated acute inflammation in experimental colitis

Kaur

Sodhi

Katyal

et al. 2015

Colloids and Surfaces B: Biointerfaces

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“…Although rectal delivery is recommended as the first-line treatment for patients with mild to moderate distal colitis, rectal administration of drugs to treat IBD is less favorable than oral administration or IV injection. [115][116][117] Despite this, many antisense oligonucleotide (ASO) medications have been successfully delivered by rectal administration in preclinical and clinical IBD studies. For example, researchers used rectal administration of galactosylated low molecularweight chitosan (gal-LMWC) and TNF-α ASO to deliver the latter into activated colonic macrophages, significantly reducing colonic TNF-α in mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis.…”

Section: Other Delivery Routesmentioning

confidence: 99%

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

Yang¹,

Merlin²

2019

IJN

117

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Inflammatory bowel disease (IBD), which mainly consists of Crohn's disease and ulcerative colitis, is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The traditional treatment strategies relied on frequent administration of high dosages of medications, including antibiotics, non-steroidal anti-inflammatory drugs, biologics, and immunomodulators, with the goal of reducing inflammation. Some of these medications were effective in alleviating the early-stage inflammatory symptoms, but their long-term efficacies were compromised by the accumulation of toxicities. Recently, nanoparticle (NP)based drugs have been widely studied for their potential to solve such problems. Various mechanisms/strategies, including size-, charge-, pH-, pressure-, degradation-, ligand-receptor-, and microbiome-dependent drug delivery systems, have been exploited in preclinical studies. A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs. Therefore, there is still a need for rationally designed and stable NP drug delivery system that can specifically target drugs to the disease site, prolong the drug's residence time, and minimize systemic side effects. This review will analyze the current state of the art in NP-mediated drug delivery for IBD treatment. We will focus on topics such as deliverable targets (at the tissue or cellular level) for treating inflammation; the target-homing NP materials that can interact with such targets; and the major administration routes for treating IBD. These discussions will integrate notable trends in the research and development of IBD medications, including multi-responsive NP-mediated delivery and naturally-derived targeting NPs. Finally, current challenges and future directions will be presented in the hopes of advancing the study of NP-mediated strategies for treating IBD.

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“…Although no related drug products are found on the marketplace, colon delivery approaches that leverage physiological parameters other than the luminal pH have been proposed and extensively studied (Gazzaniga et al, 1994;McConnell et al, 2009;Pinto, 2010;Wolk et al, 2013). Among these, the time-dependent strategy exploits the small intestinal transit time (SITT) (Davis, 1985;Gazzaniga et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

In vitro and human pharmacoscintigraphic evaluation of an oral 5-ASA delivery system for colonic release

Foppoli

Moutaharrik

Melocchi

et al. 2019

International Journal of Pharmaceutics

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5-aminosalicylic acid (5-ASA) is the most widely used drug for the treatment of ulcerative colitis. The benefits of targeted delivery of 5-ASA to the large intestine are well known, resulting in reduced systemic absorption and increased local concentrations at the disease site. In the present study, a 5-ASA colon delivery system based on the time-dependent strategy, exploiting the relatively consistent small intestinal transit time (SITT), was manufactured and evaluated in vitro as well as in vivo. The system was obtained by successive spray-coating of an immediate-release tablet core with lowviscosity HPMC and Eudragit  L. The enteric film was effective in preventing release during the acidic stage of the in vitro test, while the HPMC coating brought about reproducible lag phases prior to release in phosphate buffer medium. A γ-scintigraphy investigation pointed out that, following administration to fasted and fed volunteers, disintegration of the units never occurred prior to colon arrival. In all cases, a lag time preceded the appearance of the drug and its N-acetyl metabolite in the bloodstream, which was found to correlate with the time of disintegration in a linear mode. The plasma levels of the drug and metabolite as well as their cumulative urinary recovery were relatively low with respect to those reported when 5-ASA is delivered to the small bowel.

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New targeting strategies in drug therapy of inflammatory bowel disease: mechanistic approaches and opportunities

Cited by 23 publications

References 132 publications

Wheat germ agglutinin anchored chitosan microspheres of reduced brominated derivative of noscapine ameliorated acute inflammation in experimental colitis

Wheat germ agglutinin anchored chitosan microspheres of reduced brominated derivative of noscapine ameliorated acute inflammation in experimental colitis

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

In vitro and human pharmacoscintigraphic evaluation of an oral 5-ASA delivery system for colonic release

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