Gelatin Nanoparticles as a Modern Platform for Drug Delivery - Formulation Development and Immunotherapeutic Strategies
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Beschreibung
Nanoparticles are under comprehensive investigation as a promising platform for drug delivery since three decades. However, the transition from encouraging pre- clinical research to clinical studies and finally regulatory approval has not yet occurred for solid colloidal nanoparticles. This work shall contribute to bridging that gap. Convinced that therapeutic nanoparticulate formulations should be as extensively characterized and be kept as simple as possible, this thesis exemplarily describes analytical methods and production improvements for gelatin nanoparticles (GNPs) and proposes their employment in a variety of immunotherapeutic applications.
Up-scaling of the original manufacturing setup was technically enabled and resulted in ten-fold increased batch sizes. Systematic correlation studies facilitated the establishment of a set of equations to predict necessary GNP preparation parameters for each relevant batch size. This shall contribute to future higher GNP demand in clinical manufacturing.
Moreover, the feasibility of replacing well-established but initially toxic starting material glutaraldehyde as a cross-linking agent by the enzymatic alternative transglutaminase was demonstrated. Transglutaminase-crosslinked GNPs featured narrow particle size distributions and high storage stability.
Ultrasonic resonator technology was demonstrated as a capable tool in relative GNP size analysis and DNA surface binding detection which could serve in future as a non-destructive tool for online in-process control in continuous GNP production. Within this study, a discriminative response of cationized and non- cationized GNPs towards distinctive buffers was observed. The swelling and size reduction was found to be in accordance with the sequence of salts of the Hofmeister series.
Nanoparticles are under comprehensive investigation as a promising platform for drug delivery since three decades. However, the transition from encouraging pre- clinical research to clinical studies and finally regulatory approval has not yet occurred for solid colloidal nanoparticles. This work shall contribute to bridging that gap. Convinced that therapeutic nanoparticulate formulations should be as extensively characterized and be kept as simple as possible, this thesis exemplarily describes analytical methods and production improvements for gelatin nanoparticles (GNPs) and proposes their employment in a variety of immunotherapeutic applications.
Up-scaling of the original manufacturing setup was technically enabled and resulted in ten-fold increased batch sizes. Systematic correlation studies facilitated the establishment of a set of equations to predict necessary GNP preparation parameters for each relevant batch size. This shall contribute to future higher GNP demand in clinical manufacturing.
Moreover, the feasibility of replacing well-established but initially toxic starting material glutaraldehyde as a cross-linking agent by the enzymatic alternative transglutaminase was demonstrated. Transglutaminase-crosslinked GNPs featured narrow particle size distributions and high storage stability.
Ultrasonic resonator technology was demonstrated as a capable tool in relative GNP size analysis and DNA surface binding detection which could serve in future as a non-destructive tool for online in-process control in continuous GNP production. Within this study, a discriminative response of cationized and non- cationized GNPs towards distinctive buffers was observed. The swelling and size reduction was found to be in accordance with the sequence of salts of the Hofmeister series.
Autor*in
Sebastian Fuchs