Biomimetic engineering and imaging

 

  Our past and future research is chiefly focused on different ways and means on how drugs can be protected and delivered in different environments of the human body.

 

  In particular, we are interested in the design of non-invasive, real-time detection methods and the development   of innovative biomimetic drug carriers, which harness mechanisms present in nature to enable selective delivery of therapeutics.

Extracellular vesicles

 

  We are currently extending the idea of protecting and delivering therapeutic agents by exploring the potential of extracellular vesicles (EVs) as smart drug carrier systems. These cell-derived particles are produced by almost all cells in vitro and in vivo and they are known to be conveyors of cell-to-cell communication (Fuhrmann and Herrmann et al., Nano Today (2016)).

 

  In addition, EVs feature a natural composition, stability in physiological fluids and can potentially bypass immune activation rendering them promising drug transporters. Nevertheless, efficient methods to load small molecule drugs into EVs need to be explored in order to harness their exceptional properties (Fuhrmann* et al., J Control Release (2016)).

 

  We have shown that EVs could successfully be loaded with drugs of different hydrophobicity, which represents an essential step to develop them in a therapeutic setting. Moreover, EVs are able to deliver their cargo efficient and at the cellular level indicating their significance as smart drug carriers.

Outer membrane vesicles

 

  Most recently, we are focussing on characterising and understanding bacterial outer membrane vesicles (OMVs). These bacterial EVs are also important key mediators of interaction between bacteria and host cells. We have recently discussed they diagnostic and therapeutic potential (Fuhrmann* et al., EJPB (2017))

 

   We aim at understanding OMVs' role during infection and how they could potentially applied for novel treatment avenues.

Polymer-enzyme conjugates

 

  The gastrointestinal system represents a particularly harsh milieu in which proteins are degraded by proteases and extreme variations of pH (Fuhrmann et al., Pharm Res (2014)). We have developed an innovative approach for the stabilisation of therapeutic enzymes after oral ingestion. For this, a novel non-invasive assay to evaluate oral exogenous enzymes in vivo was designed (Fuhrmann et al., Proc Natl Acad Sci (2011)). This assay represents the first-time description of the real time measurement of activity of therapeutic enzymes in the gastrointestinal tract using coeliac disease as model disease (i.e., an inflammatory disease of the small intestine (Pinier and Fuhrmann et al., Am J Gastroenterol (2010)).

 

  We have recently discussed how polymer modification of therapeutic peptides and proteins may enhance their stability in the gastrointestinal tract (Fuhrmann et al., Curr Opin Colloid Interface Sci (2017)). Taking advantage of this principle, we have modified therapeutic enzyme with architecturally and functionally diverse polymers and evaluated them using our non-invasive in vivo imaging assay (Fuhrmann et al., Nat Chem (2013)). It was shown that modification of the endopeptidase induced stabilisation of the enzyme and unprecedented sustainment of the gastrointestinal activity in vivo. Our findings create a strong basis for the development of therapeutic enzymes for oral administration using simple and straightforward methods.

FUHRMANN | LAB

Helmholtz-Centre for Infection Research

 

Helmholtz-Institute for Pharmaceutical Sciences Saarland (HIPS)

 

Saarland University Campus E8.1
66123 Saarbrücken

Germany

Our research is supported by the NanoMatFutur programme from the Federal Ministry of Education and Research (BMBF). Project BEVA

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