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Ergebnisse nach Hochschule und Institut
Publikation Matrix Metalloprotease Triggered Bioresponsive Drug Delivery Systems–Design, Synthesis and Application(Elsevier, 10/2018) Nultsch, Kira; Germershaus, OliverEngineering of drug delivery systems has evolved in recent decades from comparably simple designs that merely controlled drug release to complex, often multistage systems that respond to multiple biological or environmental stimuli. Matrix metalloproteases (MMPs) are a family of proteolytic enzymes that are involved in numerous physiologic and pathophysiologic processes, including cancer. Therefore, these enzymes represent highly relevant targets for the development of novel bioresponsive drug delivery systems. The first part of this review summarizes major developments of the various types of MMP responsive drug delivery systems that have been achieved in the last decade and highlights promising strategies. The selection and incorporation of MMP sensitive elements into drug delivery systems as well as the interaction between MMP, drug delivery system and drug require additional scrutiny to avoid common pitfalls. Thus, the second part of this review focusses on strategies for successful selection and incorporation of MMP sensitive elements and on important design parameters related to the drug delivery system and the drug. This review will therefore provide a broad overview of successful MMP-sensitive drug delivery system designs and will inform about important design criteria for novel systems.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Novel polyurethane matrix systems reveal a particular release mechanism for sustained drug delivery by imaging and computational modeling(Springer, 2017) Campinez, Maria Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, MartinThe aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.01A - Beitrag in wissenschaftlicher Zeitschrift