Subproject: Scale-up of biotransporter production and characterization#
BioTransporters: Efficient drug delivery in biological systems
In order to maximize the therapeutic potential of an active ingredient while minimizing side effects due to excessive dosages or effects on unaffected tissues, a drug should ideally only be effective at the site of the disease. The Auto-loop project is pursuing the goal of a site-specific activation and release of drugs with the development of a biotransporter for the treatment of inflammatory diseases.
Tissue-specific release of active substances
In the course of an inflammation, specific enzymes are increasingly produced and are thus present in the inflamed tissue in an increased concentration. In healthy tissue, however, the enzymes are not present or only in low concentration. Some of these enzymes, well defined proteases, can cut proteins or peptides at a specific site. In the Auto-loop project, we will put exactly such cuttable peptide structures between the drug and a carrier polymer. If the biotransporter now enters the inflamed tissue, the structure is cut and the active ingredient is separated from the polymer – and starts working. The residence time or degradation of the biotransporter in the body is controlled via the carrier polymer.
Examples of inflammatory diseases: Achilles tendon and arteriosclerosis
One approach for the treatment of inflammation to be tested is inflammation of the Achilles tendon, which often happens to athletes. For this purpose, the biotransporter is equipped with an active substance whose potential for the repair of the tendon has already been demonstrated previously. Only at the inflamed tendon structure, the drug is released to work there.
Another indication for which a biotransporter is being developed is arteriosclerosis, which affects millions of people in Germany alone. Arteriosclerosis leads to narrowing or even occlusion of blood vessels – the result is circulatory disorders of the tissue. In conjunction with arteriosclerosis, other – but functionally analogous – enzymes are being produced that can cut the biotransporter we are developing, releasing an agent at the site of the disease.
Site-specific activation and release via click chemistry
The project partners at the University of Würzburg will equip the biotransporter at a defined point in the protein with a non-natural amino acid as the target interface to which a specific linker (anti-inflammatory and growth-promoting factors) is bound via click chemistry (EMC microcollection GmbH).
The aim of the subproject at Fraunhofer IGB is to produce the drug components of the biotransporter in larger quantities, to assess their specificity, selectivity and plasma stability as well as their immunogenicity.
The principle can be extended to other biotherapeutics, diagnostics and small drug molecules and is therefore of great strategic importance for pharmaceutical applications.