Protein-Based Nanodevices
Abstract
Rheumatoid arthritis (RA) is affecting the global population. This chronic disease can lead to serious joint damages and disabilities caused by prolonged inflammatory states with a duration from weeks to years. During these inflammatory states macrophages are playing a key role as possible distinctive markers of activation and maturation while folatereceptor beta expression rates are selectively elevated in RA synovial macrophages. Its high affinity for folic acid (FA) can be used as a strategy for targeted drug delivery to chronically activated macrophages by binding FA on the delivery particle. In this way severe side effects occurring with currently used RA treatment methods, which can be avoided by site specific drug delivery and reduced drug loading. Furthermore, decreases in the pH-value in inflammatory and cancerous tissue from pH 7.4 to pH 5.4 are reported and could serve as an additional target for a stimuli-responsive treatment strategy. Therefore, the aim of this project is the development of a bifunctional nanoparticle system for a new RA treatment strategy. On the one hand a pH-depending release profile will enable drug release only in the acidic environment of inflamed tissue while on the other hand specific targeting to chronically activated macrophages will be achieved by surface functionalization with either FA or monoclonal antibodies (mAb). Based on research results of the last decade, human serum albumin (HSA), silk fibroin (SF) and silk-elastin like proteins (SELPs) could offer nanotechnological approaches for new stimuli-responsive treatment strategies with SF and SELPs adding stimuli-responsive properties to HSA based systems. In this project HSA/silk fibroin and HSA/SELPs combinations will be investigated regarding their nanoparticle formation ability, the pH-responsive drug release behaviour and in addition the cell toxicity using various analytical methods.
keywords Protein Biochemistry
Publikationen
Project staff
Doris Ribitsch
Priv.-Doz. Mag. Dr. Doris Ribitsch
doris.ribitsch@boku.ac.at
Tel: +43 1 47654-97485
Project Leader
04.10.2019 - 30.09.2019