Understanding interactions between biopolymer-based nanostructured materials and mammalian cells: Towards a more rational design of innovative nanomedicines
Prof. Dr. Francisco M. Goycoolea
To understand how “soft” nanobiomaterials harnessed from biocompatible polymers interact with complex biological systems lies among the major current challenges in nanomedicine and nanobiotechnology. Drug delivery platforms based on nanoparticles comprising biocompatible polymers and proteins have already reached approval for treatment of breast cancer (e.g. Abraxane®). However, platforms for transmucosal delivery of nanomedicines to treat pain, autoimmune and infectious diseases or for vaccination often fail to achieve a high pharmacological bioavailability and are still far from replacing currently used injection therapy. A better understanding of the fundamental aspects that govern the interaction of natural polymers (polysaccharide and proteins) and nanostructured materials derived from these is needed. This knowledge is likely to contribute elucidating the mechanisms of cellular uptake and/or transport of the bioactive molecules to the systemic circulation that currently remain but elusive.
In previous studies, we have been able to demonstrate that the viability of mammalian cells is sensitive not only to the degree of acetylation and molecular weight of chitosan, but also to the physical state of the polymer, whether dissolved, in gelled nanoparticles or confined at the surface of nanocapsules. However, it remains much to be investigated with other polysaccharides and proteins as well with other type of nanomaterials (e.g. nanofibers).
Collaboration with: Prof. Dr. Bruno Moerschbacher (WWU); Prof. Dr. Andreas Hensel (WWU); Dr. Alexandra Deters (WWU); Prof. Swamy (UH). External collaborations: Prof. Dr. Stephan Schneider (University of Mannheim); Prof. Dr. Marc Ostermeier (John Hopkins University, USA); Prof. Dr. Ioannis Chronakis (Denmark Technical University); Prof. Dr. Waldo M. Argüelles-Monal (CIAD, Mexico).
New projects in this area can be designed around the following ideas.
1. Mucoadhesive polysaccharide-protein electrostatic self-nanoassembled complexes. Polysaccharides and proteins can be tuned to design and engineer self-assembling biocompatible nanomaterials with specific physicochemical and biological properties. In this regards, it is of particular interest to identify mucoadhesive and mucus penetrating nanomaterials. Besides chitosan, that it is well established mucoadhesive aminopolysaccharide, several other polysaccharides deserve special attention in this regards, including alginates, gellan, glucomannans and karaya gum. To investigate how the mucoadhesive behavior is modified when these polysaccharides are complexed with different proteins to form a nanocomplex, is among our main interest. Besides, it is known that when proteins are complexed with other polymers, their capacity to associate lipophilic drugs increases dramatically. Drugs that deserve special attention in this regards include capsaicin, curcumin, and others such as cyclosporins and other therapeutic peptides (e.g. insulin, exenatide-4). The biophysical properties and nanostructure of these materials is known to depend on the composition and on the processing parameters, however, much more understanding is necessary to exert better control on the stability and performance of these systems in complex biological media. To this end, cellular models of different mucosal epithelia can be utilized.
2. Investigation of the fate of biopolymer-based nanomaterials during their interaction with models of cellular epithelia. In this regards, fluorescent recombinant proteins (e.g. fluorescent proteins) can be used to label the surface of nanoparticles and hence their internalization can be probed by confocal laser scanning microscopy (CSLM) and FACS and by probing the state of tight junctions is achieved by transepihelial electrical resistance measurements (TEER). In this regards, physical and mathematical models are needed that can help to describe the phenomena involved.
