for Chemical Engineering and Biotechnology eV Germany UIBK UNIVERSITAET INNSBRUCK Austria AUTH ARISTOTELIO PANEPISTIMIO THESSALONIKIS Greece UNEW UNIVERSITY OF NEWCASTLE UPON TYNE United ID: 633084
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DECHEMA - DECHEMA Society for Chemical Engineering and Biotechnology e.V. - GermanyUIBK - UNIVERSITAET INNSBRUCK - AustriaAUTH - ARISTOTELIO PANEPISTIMIO THESSALONIKIS - GreeceUNEW - UNIVERSITY OF NEWCASTLE UPON TYNE - United KingdomCU - CARDIFF UNIVERSITY - United KingdomUNAV - UNIVERSIDAD DE NAVARRA - SpainJSI - INSTITUT JOZEF STEFAN - SloveniaEVONIK - EVONIK INDUSTRIES AG - GermanyLEK - LEK FARMACEVTSKA DRUZBA D.D. – SloveniaTHIO - THIOMATRIX FORSCHUNGS UND BERATUNGS GMBH - AustriaSAGETIS - SAGETIS BIOTECH - SpainUOG - GREENWICH UNIVERSITY - United KingdomBI - BOEHRINGER INGELHEIM INTERNATIONAL GMBH – GermanyUEF - ITA-SUOMEN YLIOPISTO - Finland
PARTNERS
Opening the door to the development of efficient and cost effective nano-delivery systems, from an industrial point of view, for macromolecular drugs necessitates the enhanced permeation of nanoparticles through the mucus gel barrier. The development of mucosal nanoparticulate delivery systems for macromolecular drugs such as therapeutic peptides, oligo- and polysaccharides and DNA-based drugs only makes sense, if effective strategies are available. Therefore, the mucus gel layer barrier, consisting of highly entangled mucus glycoproteins, will have to be 'cut' by 'chemical swords' such as mucolytic agents in order to open the door to mucosally administered macromolecular drugs for systemic circulation. According to these considerations it is the mission of ALEXANDER to develop nano-delivery systems to overcome the various mucus gel barriers without destroying them. Based on results gained within this project fundamental knowledge how to overcome the mucus gel barrier in a highly efficient manner shall be provided leading to more potent mucosal drug delivery systems in general.
MISSION
The
nano
-delivery systems that can permeate the mucus gel layer and reach the epithelium in significant quantities are expected to:
Open the door for numerous
injectable
-to-
noninvasive
-conversions of macromolecular drugs such as oral insulin and EPO(-
mimetics
)
Lead to a radical improvement in the treatment of ocular diseases
Provide radical improvement in non-viral gene therapy to mucosal tissues such as the treatment of cystic fibrosis with the CFTR-gene
IMPACT
DECHEMA e.V.
Theodor-Heuss-Allee 25
60486 Frankfurt a.M./Germany
Phone: +49 (0)69/7564-0Dr. Andreas Förster, Dr. Silke Megelski, Dipl.-Chem. Nicole HeineEmail: foerster@dechema.de; megelski@dechema.de; heine@dechema.de
http://www.alexander-fp7.eu
ALEXANDER CONCEPT
Development of Ocular Delivery Systems
Task
ALEXANDER CONCEPT
Task
Approach
Task
Approach
Nanocarrier
Permeation
Studies
In Mucus Gel LayerOrientating mucus permeation studies of nanocarriers in the gastrointerestical mucosaMucolytic studies with mucus/mucin preparations Permeation studies of nanocarriers via a mucus/mucin gel layerImpact of nanocarriers on shear compliant and shear resistant mucus layer Permeation studies on cell culture systems generating a mucus layerIn vitro mucus permeation studies:Diffusion chamber studiesMucus permeation studies with freshly excised porcine mucosa with fluorescence labeled particles utilizing confocal laser microscopyMucoadhesion studies
Cytotoxicity StudiesIn vitro toxicological screeningIn vitro cytotoxicity and immunogenicity testingMacromolecular drug and carrier biodistribution,degradation and elimination in vivoIn vivo cytoxicity, immunogenicity and genotoxicity testingAcute and sub-chronic toxicity, target organ toxicityCytotoxicity screening (ATP, LDH)Cell uptakeGenotoxicity studiesImmunogenicity studiesIn vivo biodistribution and toxicity studies
APPROACH
Source: Erin_Silversmith via Wikicommons CC BY-SA 2.5
Source: via Wikicommons
CC BY-SA 3.0
Development
of
Oral
Delivery
Systems
Preparation of
nanoparticulate
macromolecular drug delivery systems
In vitro
characterization of nanoparticulate delivery systemsIn vivo studies in various animal modelsOptimization of oral delivery systems
Task
Identification of the most promising systems according to a number of assessment and selection criteria, e.g.:highly improved permeation through mucussuitability for scale upnon-toxicetc.
Approach
Task
Development
of NanocarriersSelection and synthesis of polymers and polymer-conjugatesPreparation and characterization of nanocarriersOptimization of nanocarriers
Strategies: Disulfide breaking strategyProteolytic enzyme strategy„Slippery surface stragegy“Zeta potential changing systemsThiomer systemsSNEDDS strategyThe „Helicobacter Strategy“
Polymer synthesis
Polymer synthesis
Particle
characterization
COORDINATOR
Selection
of
nanocarriers
and drug loads for ocular deliveryFormulation development and testingPharmacokinetic modelingDevelopment of quantifiation methods for in vivo studiesStability studies of the ocular delivery systemIn vivo „proof of concept“ studies