In recent decades nanodelivery systems, including solid lipid nanoparticles, have been investigated as a solution for unfavourable properties of new drugs. These systems offer numerous advantages, such as improving the bioavailability and stability of the incorporated drug and enabling targeted drug delivery even at the subcellular level. This approach of drug delivery is important for enhancing the therapeutic effects of drugs, as it allows for higher drug retention at the site of action, thereby requiring smaller doses to achieve the same effect and minimizing potential side effects caused by the nonspecific action of drugs. The aim of master's thesis was to develop a preparation process of solid lipid nanoparticles based on the sonication method, to produce a stable dispersion of solid lipid nanoparticles with incorporated model mitochondria-targeting drug. Glyceryl behenate was used as the primary lipid component for the solid lipid nanoparticles, and prepared aqueous dispersions were stabilized with the addition of neutral or positively charged surface-active agents. Two different formulations were prepared; the first with the solution of two neutral stabilizers, namely poloxamer 188 and polysorbate 80, while the second included an additional positively charged stabilizer, namely N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride. The average hydrodynamic size of negatively charged nanoparticles (~ -7 mV) was ~190 nm, while the positively charged nanoparticles (~ +25 mV) were smaller (~105 nm). The positively charged nanoparticles proved to be more stable during storage at 4°C, maintaining a similar hydrodynamic size without visual changes even after 60 days of storage, whereas the hydrodynamic size of the negatively charged nanoparticles increased significantly between the 7 and 14 days of storage. We demonstrated that the storage temperature significantly affects the stability of the prepared solid lipid nanoparticles, with dispersions being more stable at lower temperatures. We successfully incorporated the model mitochondria-targeting drug into both types of nanoparticles, achieving the drug content of ~5%, and the encapsulation efficiency slightly over 40% for both types of nanoparticles. The incorporation of the drug into the solid lipid nanoparticles slightly reduced their stability during their storage at 4°C. Within our study we successfully developed the procedure for the preparation of stable solid lipid nanoparticle dispersions with incorporated model mitochondria-targeting drug.
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