Biopta is able to predict drug effects in the stomach, small intestine or large intestine providing valuable information on safety or efficacy.
- Changes in motility
- Pro- or anti-inflammatory activity
- Drug absorption
Therapeutic Areas
In vitro assays in human tissue can be used to investigate healthy tissues or diseased tissues.
The following therapeutic areas are most commonly investigated:
- Inflammatory bowel diseases
- Irritable bowel syndrome GI motility assays: an in vitro indicator of gut transit time (TT)
Biopta is able to study isolated sections from most regions of the GI tract. The GI tract is one of the most highly innervated organs of the body and the control of motility is the result of a complex interplay between local and central neural and humoral factors.
The enteric nervous system is often called the “mini-brain” because local control involving sensory neurons, ascending and descending interneurons and motorneurons are all present within the submucosal plexus and myenteric plexus. Much of the regulation of GI motility therefore occurs locally and the effects of test compounds that promote or inhibit motility can be investigated in isolated segments of GI tissue.
Isolated sections of the stomach, small intestine or large intestine can be used to investigate:
- Direct effects of test compounds on intestinal tissue.
Some drugs that act directly on smooth muscle cells can increase or decrease tone within the GI tract which may act to increase or decrease motility · Interactions of test compounds with neuronal reflexes.
Rather than a direct effect on smooth muscle, it is more common for drugs to alter motility through changes in neuronal function. For example, many drugs in development for irritable bowel syndrome target the 5-HT4 receptor which promotes the release of acetylcholine from cholinergic motorneurons and thereby increases GI motility.
Biopta is able to stimulate the nerves present in isolated tissue and observe changes in motility in the presence and absence of test compounds. Mucosal Organoculture The mucosal lining of the GI tract is a secretory and absorptive membrane, which also plays important sensory and protective roles in the healthy gut.
Inflammation of the mucosa is a defining feature of many GI disorders, most notably Crohn’s disease and ulcerative colitis. Biopta is able to obtain both normal and inflamed GI tissues and can culture explants of mucosa in order to examine the production of cytokines or other endogenous mediators or to examine changes in cell type or microanatomy.
Prediction of Gut Permeability (Pe) using Human Small Intestine
Candidate oral drugs should display high bioavailability, but in order to select the best candidates and most appropriate doses, accurate prediction of gastrointestinal permeability is essential.
Current in vitro methods for the prediction of gut permeability are often unsatisfactory. Systems such as the Caco-2 cell line, MDCK cells, artificial cell membranes or 2/4/A1 cell line (rat small intestinal cell line) are often reasonable at predicting the permeability of passively absorbed compounds that have high permeability; however, they are inaccurate when used to predict the absorption of compounds that are actively absorbed by the gut or compounds that are poorly absorbed.
Human intestinal cells (enterocytes) express different types and amounts of transporters from other species and even human cell lines such as Caco-2 (a colon cancer cell line that has been transformed and more closely resembles enterocytes than colonocytes) do not accurately reflect the expression patterns of human small intestine. Most drugs in development are stable within the GI fluids and the determination of oral bioavailability is therefore dependent on the dissolution of the drug within the GI fluids (drugs with poor dissolution may enter the large intestine) and their permeability within the GI tract. Biopta uses intact human small intestine, where the majority of drugs are absorbed, to predict the permeability of test compounds.