Entwicklung von PLGA-Nanopartikeln als Drug Delivery System für lipophile Wirkstoffe, die in die Arachidonsäurekaskade eingreifen

In the present work, an innovative drug carrier system for two lipophilic natural substances (embelin and retinol) based on PLGA nanoparticles was developed. Loading efficiency, stability and release of the active ingredients were modified and optimized by modifying the nanoparticles with albumin or chitosan. By loading natural substances with an anti inflammatory effect into these drug carrier systems presented, a further treatment option for chronic inflammatory bowel diseases could be developed. Especially with regard to physicochemical stability, storability and controlled release of the active ingredients, it could be shown that loading embelin and retinol in PLGA nanoparticles can be advantageous. The parameters of the particle formation were optimized with regard to the rotation speed of the homogenizer, concentration of the emulsifier, reaction temperature and centrifugation speed during the purification, and the nanoparticles were characterized in terms of morphology, physicochemical properties and their toxicological profile. The optimized manufacturing method allowed the formulation of PLGA nanoparticles with a diameter in the size range of 200 nm and a narrow particle size distribution. Furthermore, loaded PLGA nanoparticles with albumin or chitosan modification were developed for both natural products, which met the quality requirements with regard to particle size and distribution. A manufacturing method has been developed for retinol that enables the nanoparticle formation under the exclusion of light and atmospheric oxygen. This improved the loading efficiency of retinol. The successful modification of the nanoparticles with albumin or chitosan made it possible to control the physicochemical properties, the morphology, the loading efficiency and the toxicological profile of the particles.


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