Dokument

Summary:
With an objective of designing gelatin based nanoparticulate delivery system for macromolecules, some of the important challenges associated with gelatin nanoparticles are addressed in this thesis. The first goal is to avoid aggregation, one of the most often encountered problems during nanoparticle formation from gelatin. In this context, different parameters involved in nanoprecipitation technique are investigated, in order to obtain optimum preparative conditions. Effective loading of FITC-dextran as a model hydrophilic macromolecule shows good potential of the system for macromolecular drugs. Attempts are also made to modify the surface of gelatin nanoparticles with PEI, in order to facilitate surface adsorption of negatively charged macromolecules. However, the size of nanoparticles is substantially increased after PEI coating. Moreover, the particles strongly positively charged particles showed an increased toxic behavior after surface modification with PEI. The second main challenge in gelatin nanoparticles is the use of crosslinkers for stabilization of particles. Since crosslinkers not only crosslink gelatin but also the active sites of therapeutic proteins, this may lead to biological inactivity of proteinaceous compounds. Therefore, we introduce an alternative approach of stabilization. Gelatin nanoparticles are entrapped in nanospheres made of synthetic polymers, using a unique technique of nanoprecipitation-emulsion solvent evaporation. PLGA seems to be ineffective, while Eudragit® E100 efficiently entraps gelatin nanoparticles in nanosphere matrix depending on concentration.

Bibliographie / References

1. Saeed Ahmad Khan, Marc Schneider, Improvement of Nanoprecipitation Technique for Preparation of Gelatin Nanoparticles and Potential Macromolecular Drug Loading. Macromolecular Bioscience,2013, 13(4):455-63.
2. Saeed Ahmad Khan, Marc Schneider, Stabilization of gelatin nanoparticles without crosslinking, Submitted. Macromolecular Bioscience, submitted.
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7. Poster Presentation
8. Saeed Ahmad Khan, Marc Schneider, Nanoprecipitation versus two step desolvation technique for the preparation of gelatin nanoparticles, SPIE conference proceedings volume:8595 (Colloidal Nanocrystals for Biomedical Applications VIII, 2013).
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12. Saeed Ahmad Khan, Marc Schneider, Crosslinked gelatin nanoparticles for the delivery of macromolecules, CRS local chapter meeting, 27-28 Feb. 2014, University of Kiel, Germany.
13. Delivery of antibiotics by nanospheres prepared by MJR technology (with MJR PharmJet GmbH, in preparation).
14. Saeed Ahmad Khan, Marc Schneider, Effect of molecular weight on encapsulation and release of macromolecular drugs from gelatin nanoparticles, 10 th international conference and workshop on Biological Barriers, 16-21 February 2014, Saarland University, Germany.
15. Saeed Ahmad Khan, Marc Schneider, Gelatin nanoparticles as a potential nanocarrier for macromolecular drugs, DPhG annual conference 2013, drug delivery inspired by nature 9-11 Oct. 2013, Freiburg University, Germany.
16. Saeed Ahmad Khan, Marc Schneider, Hydrophilic nanoparticles for hydrophilic macromolecular drugs, CRS local chapter meeting, 21-22 Mar. 2013, Ludwigshafen, Germany.Clemens Tscheka, Saeed Ahmad Khan, Mohamed Tawfik, Eman Haimour, Marc Schneider, Novel filamentous Carrier Systems based on biodegradable Hydrogels, CRS local chapter meeting, 21-22 Mar. 2013, Ludwigshafen, Germany.
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