SFB 1112:  Nanocarriers: Architecture, Transport and Topical Application of Drugs for Therapeutic Use

• Subject Area: Chemistry ; Agriculture, Forestry and Veterinary Medicine ; Biology ; Medicine ; Physics
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 234930468

The Collaborative Research Center 1112 (SFB 1112) has been established as a multidisciplinary research network for preparing and characterizing drug-loaded nanocarriers in order to elucidate the fundamental mechanisms of topical therapy focusing on inflammatory skin diseases. During the first funding period joint work has yielded novel and highly efficient drug delivery systems that also included controlled and triggered drug release. This concept of joint work reached from the chemical synthesis of nanocarriers to the fundamental concepts of topical therapy. Sensitive and selective approaches to observe and model the transport pathways and drug release from nanocarriers in biological matters were investigated and the physico-chemical, pharmacological, toxicological, and dermatological properties of nanocarriers were explored. This led to a significantly improved understanding on the role of nanocarriers providing a knowledge-based foundation for improved concepts for topical therapies, which reach beyond the current dermatological state-of-the-art. In the second funding period SFB 1112 will address, besides the hydrophobic drugs tacrolimus and dexamethasone the hydrophilic substance tofacitinib and the biological etanercept for widening the scope of drugs that can be delivered by drug-loaded nanocarriers. Tailored drug carriers accommodating these drugs in a controlled and efficient way are developed, along with a well adapted variety of triggered drug release mechanisms, comprising thermal, pH- and redox-related as well as enzymatic processes, which reflect the distinct local changes of inflamed versus healthy tissue. Furthermore, mucoadhesive drug-loaded nanocarriers and aging of skin are included for widening the scope of use of drug-loaded nanocarriers. The transport pathways in biological matter, such as skin models, human and murine skin, living organisms, and the oral mucosal barrier will be observed by further improved selective and sensitive methods of spectroscopy, microscopy, and spectromicroscopy, so that the uptake and drug release can be followed in detail. Theoretical modeling will be developed further, allowing for the determination of the fundamental principles of nanocarrier transport and drug release. Pharmacological and toxicologic properties of nanocarriers are determined before in vivo, ex vivo, and in vitro approaches for testing are applied. Standard protocols for determining the physical and toxicological properties of the drug nanocarriers are refined and used along with analytical approaches as a central task of SFB 1112.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Optimization of polymer and lipid nanocarriers and nanocrystals/particles for dermal delivery (Project Head Bodmeier, Roland )
• A02 - Core-multishell nanocarriers for drug delivery into skin (Project Head Haag, Rainer )
• A03 - Supramolecular approaches for phase organization, particle formation, disintegration, and drug binding capacity in depsipeptide-based nanocarriers (Project Heads Lendlein, Andreas ;  Neffe, Axel T. )
• A04 - Environmentally responsive nanogels for drug delivery (Project Heads Calderón, Marcelo ;  Haag, Rainer )
• B01 - EPR spectroscopic investigations on drug delivery and release of nanocarriers into excised skin and 3D-skin models (Project Heads Bittl, Robert ;  Meinke, Martina )
• B02 - Label-free spectromicroscopy: Probing drugs and drug nanocarriers in cells, skin, and mucous membranes (Project Head Rühl, Eckart )
• B03 - Characterization of transport and release properties of responsive nanocarriers by time-resolved fluorescence spectroscopy/microscopy and localization microscopy (Project Head Alexiev, Ulrike )
• B04 - Multiscale models for carrier-assisted drug transport through skin (Project Head Netz, Roland )
• C02 - Patient-derived diseased and autologous immunocompetent skin models for the examination of drug-loaded nanocarrier systems (Project Heads Hedtrich, Sarah ;  Kleuser, Burkhard )
• C03 - Nanocarriers in the skin and oral mucosa of mouse models: Specific targeting of inflammation and role of barrier dysfunctions (Project Heads Gruber, Ph.D., Achim Dieter ;  Mundhenk, Lars )
• C04 - Impact of inflammatory microenvironment on nanocarrier penetration, drug release, and biological effects in human skin (Project Heads Blume-Peytavi, Ulrike ;  Vogt, Annika )
• C05 - Triggered release of drugs from nanocarriers within the hair follicles (Project Head Lademann, Jürgen )
• MGK - Integrated Research Training Group "Nanocarriers" (Project Head Rühl, Eckart )
• Z01 - Toxicity and analytics of native and drug-loaded nanocarriers (Project Heads Kleuser, Burkhard ;  Ma, Nan ;  Schäfer-Korting, Monika )
• Z02 - Central Tasks - CRC Head-quarter and Administration (Project Head Rühl, Eckart )

• Applicant Institution: Freie Universität Berlin
• Participating Institution: Charité - Universitätsmedizin Berlin; Helmholtz-Zentrum hereon GmbH; Institut für Aktive Polymere
• Participating University: Humboldt-Universität zu Berlin; Universität Potsdam
• Spokesperson: Professor Dr. Eckart Rühl