Gelatin Nanoparticles as Potential Nanocarriers for Macromolecular Drugs

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 nanoparticl...

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1. Verfasser: Khan, Saeed Ahmad
Beteiligte: Schneider, Marc (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2014
Pharmazeutische Technologie und Biopharmazie
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Zusammenfassung: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.
DOI:https://doi.org/10.17192/z2014.0380