Chiral self-assembly in bile salt sequestrants and in drug delivery

The diseases bile salt (BS) malabsorption and hypercholesterolemia are both treated using BS sequestrants – polymers that bind excess BS in the intestine.

Oppositely charged polymers and BS surfactants interact strongly in water causing a spontaneous formation of supramolecular mixed complexes. These have unique structures with chiral functionality that are important for biomedical applications.

The proposed research project aims to provide fundamental understanding on the intermolecular interactions in mixtures of biocompatible oppositely charged polymers and BSs in order to identify new BS sequestrants and novel polymer-BS based carriers for chiral drugs.

Stimuli-responsive block copolymers and cellulose-based polymers will be investigated and how the formation, structure and chiral properties of mixed complexes change with, e.g., temperature, pH, polymer chemistry and BS architecture.

State-of-the-art cryogenic transmission electron microscopy and tomography, X-ray, neutron and light scattering and circular dichroism spectroscopy will be employed for structural information and calorimetrical techniques will elucidate the polymer–BS interactions. The binding capacity of the polymers will be evaluated by, e.g., nuclear magnetic resonance.

The time plan includes three work packages (WP): complex formation of oppositely charged block copolymers and BSs (WP1); interactions between cellulose-based polymers and bile salts (WP2); biocompatible polymers as BS sequestrants (WP3).