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Physiologically Relevant Model Gut System

Physiologically Relevant Model of Gastrointestinal Digestion and Absorption

Quote: KT135803

The Challenge

Oral drug delivery R&D and assessment of functional foods is hampered by the lack of physiologically relevant model gut systems which capture all three of the major barriers to the effective delivery of a pharmaceutical or nutraceutical compound: digestive fluids, the mucus barrier and the epithelial barrier. Current in vitro models don't translate well to the in vivo situation, resulting in the early use of animal models, which are difficult, expensive and physiologically different to humans.
Oral drug delivery R&D needs to be cheaper, quicker, safer and more effective, therefore a technology which allows for earlier optimisation and faster selection of lead compounds is highly desirable.

The Solution

At Newcastle University we have developed a novel, integrated, in vitro model gut system (MGS) which simulates the digestive and absorptive processes of the gastrointestinal (GI) tract from mouth to terminal small intestine - something which has previously been described as the 'holy grail' of research into oral delivery. This is the first system of its kind capable of integrating a cell culture system with a physiologically accurate mucus layer and whole digestive secretions (including bile and digestive enzymes). It is the only model that allows for continuous sampling across the GI tract.
An integrated model of the digestive tract has not been possible until now as digestive fluids contain components which result in rapid cell death (bile, proteases etc), and no model has been able to replicate this protective function of mucus in vitro. We have developed a unique system for purifying and rebuilding a mucus barrier which allows us to combine a physiologically relevant mucus layer with a stable cell system. Furthermore this means we can accurately model the effect of digestive secretions, complete with digestive enzymes and bile, on drug delivery as the mucus layer affords the cells protection from these secretions, as it would in vivo. The system has 100% cell viability over a 5 hour period, and has been validated through uptake studies of labelled compounds.

This model can be used:

1. To study the chemical and enzymatic digestion of the macronutrients fat, protein and carbohydrate
2. To analyse the effects of exogenous compounds on digestion with a view to developing novel therapeutics.
3. To quantify uptake of various large and small molecules and test the efficacy of different drug delivery systems.
4. To investigate the bioavailability and regulatory activity of bioactive compounds.
5. As an early screening and development tool for oral drug delivery to test uptake and refine formulations.

The efficacy of the MGS has been demonstrated by the role it has played in building a case for the novel lipase inhibitor alginate as a weight loss treatment.
The MGS is a cost-effective and ethical alternative to animal studies and can be used as a pre-screen to inform and improve human studies which are increasingly important since the introduction of EFSA Regulations. Preliminary MGS trials provide data that can be used to investigate efficacy, dosage, delivery methods and decisions that can save costs and improve results without using animal models.

The Opportunity

This integrated gastrointestinal model is available as a contract research service for screening, developing and testing of oral formulations. This opportunity will be of interest to the pharma and biotech sectors, CROs and the food and nutraceutical industries.
Customers using the model will:

• save time and money - more compounds and concepts can be screened in vitro and compounds which are likely to fail can be rejected sooner
• benefit from the miniaturisation of the MGS - less compound is needed, further reducing cost and increasing throughput, especially at prototype stages
• be able to reduce, refine and improve costly later stage testing
• increase speed of bringing successful products to market
• improve return on R&D investment
• improve current formulations
o reduce dose, cost and side-effects
o reformulate injectables to orals

A BBSRC Follow on Fund has been secured to further develop the product. As well as the small intestinal model, a gastric model has been developed, and the research team are looking at how this approach can be applied to other mucosal surfaces.

Intellectual Property Status

Patent applications were filed under PCT and have entered the national phase (US and Europe).
Title: Model gut system
Application numbers: US (US15/039172); Europe (EP3074769)
Filing date: 21st November 2014
Applicant: University of Newcastle upon Tyne


Dr Geraint Lewis, Enterprise Team, Research & Enterprise Services, Newcastle University, Faculty of Medical Sciences, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.