Affiliation:
1. Department for Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication University of Würzburg Pleicherwall 2 97070 Würzburg Germany
2. Department of Biotechnology and Biophysics University of Würzburg Am Hubland 97074 Würzburg Germany
3. Physical Chemistry II University of Bayreuth Universitätsstr. 30 95440 Bayreuth Germany
4. Institute of Anatomy and Cell Biology University of Würzburg Koellikerstraße 6 97070 Würzburg Germany
Abstract
AbstractNanohydrogels combine advantages of hydrogels and nanoparticles. In particular, they represent promising drug delivery systems. Nanogel synthesis by oxidative condensation of polyglycidol prepolymers, that are modified with thiol groups, results in crosslinking by disulfide bonds. Hereby, biomolecules like the antidiabetic peptide RS1‐reg, derived from the regulatory protein RS1 of the Na+‐D‐glucose cotransporter SGLT1, can be covalently bound by cysteine residues to the nanogel in a hydrophilic, stabilizing environment. After oral uptake, the acid‐stable nanogels protect their loading during gastric passage from proteolytic degradation. Under alkaline conditions in small intestine the nanohydrogels become mucoadhesive, pass the intestinal mucosa and are taken up into small intestinal enterocytes by endocytosis. Using Caco‐2 cells as a model for small intestinal enterocytes, by confocal laser scanning microscopy and structured illumination microscopy, the colocalization of fluorescent‐labeled RS1‐reg with markers of endosomes, lysosomes, and trans‐Golgi‐network after uptake with polyglycidol‐based nanogels formed by precipitation polymerization is demonstrated. This indicates that RS1‐reg follows the endosomal pathway. In the following, the design of bespoken nanohydrogels for specific targeting of RS1‐reg to its site of action at the trans‐Golgi network is described that might also represent a way of targeted transport for other drugs to their targets at the Golgi apparatus.
Funder
European Regional Development Fund
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials