Solid lipid nanoparticles were developed with the aim to improve propreties of conventional lipid-based delivery systems. They are composed of biocompatible and biodegredable substances and have several advantages in drug delivery, including controlled release and targeted delivery. Due to these advantages, scientists have begun to investigate them as potential delivery systems for antigens and adjuvants. They have great potential as delivery systems for oral vaccines, which could increase patient compliance and reduce injuries during administration.
The aim of the master's thesis was to optimize the technological process of producing lipid nanoparticles for adjuvant delivery in vaccines. In the first part of the thesis, empty solid lipid nanoparticles and nanostructured lipid carriers were prepared using the method of lipid melt homogenization in an aqueous phase of stabilizers by ultrasonic homogenization. During manufacturing process, we varied the concentration, type, and ratio of stabilizers, as well as the content of liquid lipid. We studied the influence of process parameters on the properties of nanoparticles and modified the manufacturing process to obtain reproducible series of solid lipid nanoparticles and nanostructured lipid carriers with appropriate size and size distribution. The particles were then seperated from the dispersion medium using ultracentrifugation. Once we optimized the process and composition of empty lipid nanoparticles, we incorporated adjuvants for vaccines into the particles. Since we had to dissolve the adjuvant due to the manufacturing process of the nanoparticles, we also investigated the effects of selected organic solvents on the size and distribution of nanoparticles before incorporation of adjuvant. We incorporated 5 % and 2.5 % (w/w) adjuvant into solid lipid nanoparticles and nanostructured lipid carriers with 10 % (w/w) liquid lipid using ethyl acetate. However, gelation occured during manufacturing process when using ethyl acetate, so we replaced it with tetrahydrofuran. The final product consisted of solid lipid nanoparticles and nanostructured lipid carriers with 10 % (w/w) liquid ipid and with 2.5 % (w/w) adjuvant. We measured the average size and size distribution of the particles using photon correlation spectroscopy for all samples. We also measured the zeta potential of particles with incorporated adjuvant using laser Doppler anemometry.
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