26. August 2019 | Press releases:

Testing Active Ingredients and Drugs with Chip Systems New Human Nasal Mucosa and Cornea Model for Preclinical Testing of Drug Candidates

In order to advance the development and testing of new active substances and drugs, researchers at Teschniche Universität Braunschweig are working together with their partners on innovative test systems. In one project, a corneal model is being adapted to meet the high regulatory requirements for drug testing against eye diseases. In another project, a human nasal mucosa is simulated on a chip system. The two test systems promise more reliable results than conventional methods and help to replace and avoid animal testing. The TU Braunschweig will receive funding for both research projects in the BMBF funding priority “Alternative methods to Animal Testing” amounting to around 710,000 euros for three years.

Two projects at TU Braunschweig are investigating new testing methods in order to test drug candidates and drugs without animal testing or the removal of animal tissue and at the same time obtain more reliable information on bioavailability in the human organism. The Institute of Pharmaceutical Technology and the Institute of Microtechnology rely on organ-on-a-chip systems and cell cultures that simulate dynamic processes in the eye and nose better.

In the “Ocular DynaMiTES” project, funded by the German Federal Ministry of Education and Research (BMBF) with 321,000 euros, an artificial cornea is to be further developed as a model so that drugs can be reliably tested for application to the eye. In the “NasaMuc” project, a joint project with the company InSCREENeX, a nasal mucosa model is being researched in order to test new dosage forms and improve the efficacy of drugs. For this the TU Braunschweig will receive funding of 390,000 euros from the BMBF.

“Ocular DynaMiTES” – Artificial Cornea

The development of new and cost-effective drugs plays an increasingly important role in our aging society. In the area of age-related diseases, an increase in eye diseases is to be expected, e. g. due to diabetes. One of the greatest challenges in drug development is that the drug candidates arrive and remain in the eye at the desired site of action and in the required concentration. This is made more difficult by the high barrier function of the cornea, the natural flow of tears and the eyelid movement. Studies are currently being conducted on removed corneas or directly on laboratory animals. Over the past 15 years, this has led to the development of cell culture-based cornea models with comparable properties to human corneal tissue. However, it has been shown that static experimental conditions in many cases led to misinterpretations of the data.

In a proof-of-concept study, researchers at Technische Universität Braunschweig were able to show that a microfluidic system (DynaMiTES – Dynamic Micro Tissue Engineering System) is able to simulate the dynamics of the eye better than static experimental set-ups. For example, the barrier function of the human cornea and processes at the eye surface can be reproduced. “With this experimental set-up, the significance of in vitro experiments can be drastically increased and the model can thus be accepted by the authorities,” says Prof. Stephan Reichl from the Institute of Pharmaceutical Technology. BMBF funding will be used to validate the developed cell-based, dynamic in vitro test system for substances (primarily drug candidates).

Nasal mucosa model – nasal cells on microfluidic chip systems

The proportion of active substances among newly developed drug candidates that can be regarded as biopharmaceutically problematic is estimated at around 75 percent. The main problems are their lack of water solubility, low ability to penetrate biomembranes or low stability in the gastrointestinal tract. For many active substances, it is therefore necessary to consider alternative dosage forms. The application of active substances via the nasal mucous membrane (nasal mucosa) offers some advantages over oral administration, for example the cell layer in the nose is more permeable than that in the intestine, the stability of sensitive active substances is sufficiently high, and the excellent blood circulation of the nasal tissue enables rapid removal to the site of action.

At present, studies to assess the absorption of active substances via the nose are usually carried out on laboratory animals or on removed animal tissues. “To date, no valid alternative test system for the human nasal mucous membrane is available. The goal of “NasaMuc” is therefore the development of a cell-based in vitro test system,” says Professor Andreas Dietzel. This test system will be used to analyse the uptake of drug candidates through the mucous membrane without having to resort to animal or animal tissue experiments.

In order to meet the high demands placed on the test system for drug development, scientists are working together in a joint project: In addition to the Institute of Pharmaceutical Technology and the Institute of Microtechnology, InSCREENeX GmbH, an spin-off company of the Helmholtz Centre for Infection Research (HZI), is also involved.