Ass.-Prof. Dr. Gergely Kali
Polymers for Biomedical Applications
The working group's focus is on an interdisciplinary research area at the intersection of polymer chemistry, polysaccharides, supramolecules, and drug delivery. Our work includes polymer and supramolecule synthesis using modern controlled polymerization techniques, functionalization of various macromolecules with biorelevant moieties, as well as drug delivery studies.
Two main drug delivery routes are examined. The first is the mucosal route, utilizing mucoadhesive materials like thiolated, unsaturated, and cationic oligomers and polymers. This pathway is especially important because several key active pharmaceutical ingredients have short residence times on the mucosa-covered absorption membranes (for example, in the gastrointestinal tract), leading to low systemic absorption or limited local effects. Cellular uptake enhancements with similarly functionalized macromolecules are also investigated.
These novel polymers are safe, show potential for drug delivery, and enhance patient comfort.
Cyclodextrins are cyclic oligosaccharides already widely used in biomedicine. We modify these macrocycles to improve mucoadhesive properties, enhance membrane permeability, or increase cellular uptake. Thiolated cyclodextrins are primarily synthesized through two reaction pathways. A high degree of thiolation can be achieved through reaction with phosphorus pentasulfide. With this method, complete thiolation is possible. S-acetyl-mercaptosuccinic anhydride forms ester bonds with hydroxyl groups, providing both thiolation and high aqueous solubility.
Other functionalizations of cyclodextrins, such as derivatization with cationic or unsaturated groups, are also of interest to us.
Several other polysaccharides, including starch, cellulose, chitosan, and carrageenan, are also used in these reactions.
Polymers are mainly synthesized using reversible deactivation radical polymerization techniques such as Atom Transfer Radical Polymerization (ATRP) or Reversible Addition-Fragmentation Chain Transfer (RAFT). Sulfhydryl groups or unsaturated functionalities are employed to add mucoadhesive properties or enhance the cellular uptake of these excipients.
Our research focuses on innovative drug delivery systems made from synthetic polymers. Polymerizing myrcene, a monoterpenoid, produces a material with a controlled microstructure and mucoadhesive properties. These polymers also exhibit antioxidant and antimicrobial activities. Consequently, we refer to them as Active Pharmaceutical Excipients. Polycondensation of PEG with mercaptosuccinic acid or maleic anhydride, combined with model drugs, creates a mucoadhesive polymer containing in-chain polymerized active pharmaceutical ingredients. This material offers sustained drug release at the application site.
Polyrotaxanes are supramolecular polymer assemblies made up of polymeric axes and threaded macrocycles. We synthesize these materials to enhance the cellular uptake of the macrocycles and reduce their membrane-damaging effects.
We investigate the synthesis possibilities of polyrotaxanes using threading and rotaxa-polymerization methods. Our main goal is to understand how functional groups affect the cellular uptake of polyrotaxanes and to identify potential degradation pathways in the cytosol that result in the release of macrocycles.