Matrices for combined delivery of proteins and synthetic molecules.

With the increasing advancement of synergistic, multimodal approaches to influence the treatment of infectious and non-infectious diseases, we witness the development of enabling techniques merging necessary complexity with leaner designs and effectiveness. Systems- and polypharmacology ask for multi-potent drug combinations with many targets to engage with the biological system. These demand drug delivery designs for one single drug, dual drug release systems and multiple release matrices in which the macromolecular structure allows for higher solubilization, protection and sequential or combined release profiles. As a result, nano- and micromaterials have been evolved from mono- to dual drug carriers but are also an essential part to establish multimodality in polymeric matrices. Surface dynamics of particles creating interfaces between polymer chains and hydrogels inspired the development not only of biomedical adhesives but also of injectable hydrogels in which the nanoscale material is both, adhesive and delivery tool. These complex delivery systems are segmented into two delivery subunits, a polymer matrix and nanocarrier, to allow for an even higher tolerance of the incorporated drugs without adding further synthetic demands to the nanocarrier alone. The opportunities in these quite novel approaches for the delivery of small and biological therapeutics are remarkable and selected examples for applications in cancer and bone treatments are discussed.

Formation of ß-sheets in glutamine and alanine tripeptides.

The misfolding and aggregation of proteins is associated with many different diseases including the trinucleotide repeat disorders and Prion diseases. We have studied three residue peptides comprising alanine and glutamine in order to understand the short range interactions affecting the formation of ß-rich aggregates. Using infrared spectroscopy, we have found that trialanine and triglutamine form significant amounts of ß-sheet, but that tripeptides containing alanine and glutamine are only able to form ß-sheet if the glutamine side-chains extend outward on both faces of the sheet. From our data, we conclude that different stabilizing interactions are responsible for ß-sheet formation in trialanine and triglutamine.