Aminosalicylate R&D for IBD

Aminosalicylates, in particular the original sulfasalazine (SASP) and other formulations containing 5-aminosalicylic acid (5-ASA), are one of the earliest treatments for inflammatory bowel disease (IBD). It is interesting that almost all these agents affect IBD inflammation in one or more of the many points at which it has been special reported to possible play a role (e.g., induction on arachidonic acid metabolism, ROS scavenging, and effects on the function of white blood cells and the production of cytokines). One of the most commonly used class is aminosalicylates as they have little side effects and highly safe. The emergence of newer aminosalicylates, coupled with an improved understanding of the pathogenesis and therapeutics for IBD may enable wider application in various forms as well as stages of IBD.

Fig. 1. A description of the mechanism of action of mesalazine in the colon. Fig. 1. The mechanism of action of mesalazine in the colon. (Nielsen et al., 2007)

Aminosalicylate R&D Services

At Ace Therapeutics, we provide tailored aminosalicylate development services to help clients with their IBD drug discovery efforts. Our team of trained experts who have extensive experience in the IBD inflammatory cascade, can offer full range solutions for each stage of aminosalicylate development.

Mechanism of Action Analysis for Aminosalicylates

We provide information on the mechanism of action and key targets regarding SASP/5-ASA anti-inflammatory effects at colon. These studies are supported by multiple functional, pharmacological and chemical lines of evidence and confirmed in animal models of IBD. We can explore several mediators within the inflammatory cascade that may play a role in pathophysiology of IBD-related inflammation happening inside intestinal wall of animals

Activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) and its expression
Scavenging of reactive oxygen species
Inhibition of Interleukin 1 (IL-1) and tumor necrosis factor (TNF)
Inhibition of prostaglandin and leukotriene
Apoptosis induction
Inhibition of nuclear factor κB (NF-κB) activity
Induction of regulatory T cells (Treg) in the colon

Development of Novel Formulations for 5-ASA

5-ASA being absorbed so completely in the upper jejunum that significant amounts of active compound cannot reach the colon. Based upon our drug chemistry and delivery platform experience, we are able to create innovative formulations of 5-ASA tailored for the treatment of IBD as required by our customers.

Novel Formulations	Details
pH-dependent formulations	We work with our clients to develop formulations tailored for pH dependent release of 5-ASA in the distal ileum and colon, while minimizing systemic exposure.
Microspheres and nanoparticles	And we are able to make 5-ASA micropellets or nanoparticles part of microsphere formulations, so that such corticosteroids can be targeted into the inflammatory tissues as well.
Dosage forms	We can develop various dosage forms of 5-ASA, including suppositories, foams, and enemas. This approach enables delivery of 5-ASA immediately to the inflamed mucosa at concentrations far exceeding that possible via oral therapy.

Ace Therapeutics provides reliable strategies to help clients develop aminosalicylic acid preparations. We partner with academic and pharmaceutical collaborators to develop controlled studies of preclinical IBD. Do not hesitate contact us. We are definitely seeking forward to receiving associated with you.

Reference

Nielsen, O. H., & Munck, L. K. (2007). Drug insight: aminosalicylates for the treatment of IBD. Nature clinical practice Gastroenterology & hepatology, 4(3), 160-170.

! For research use only, not intended for any clinical use.