Melt-emulsified nanoparticles based on at room temperature solid lipids are described in the literature as effective drug carrier systems. For these solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) improved bioavailability, protection of sensitive drug molecules from the environment (water, light) and controlled release characteristics have been claimed. Successful incorporation not only of lipophilic, but even of hydrophilic drug molecules has been postulated. In preferred scenarios, (1) the solid lipid matrix forms nanospheres (SLN) or (2) nanostructured droplets of liquid lipids are distributed within the solid lipid nanospheres (NLC), respectively. Accordingly, both types of nanoparticles would provide a control of drug release (due to the encapsulating solid lipid) and even a higher incorporation capacity for NLC (due to the liquid lipid with improved solubilization capacity for lipophililic host molecule). In this thesis on hand, by physicochemical characterizations detailed knowledge was gained concerning the drug localization in SLN, drug and oil localization in NLC, particle shape of SLN and NLC, accessibility of surrounding aqueous phase to the incorporated drug, and the behavior of lipid nanodispersions on human skin (ex vivo). Non-invasive investigation techniques have been applied whenever possible. Nuclear magnetic resonance (1H-NMR) and electron spin resonance spectroscopy (ESR), fluorescence spectroscopy, X-ray diffraction, measurements of refractive index and density, and Raman spectroscopy were used beside invasive methods (transmission electron microscopy (TEM), field-flow fractionation (FFF), differential scanning calorimetry (DSC), photon correlation spectroscopy (PCS) and laser diffraction (LD)). Summarizing, this thesis reveals the common theory of drug localization in the solid lipid particle (SLN) as well as the incorporation of oily domains in the particles (NLC). The results indicate that the studied colloidal lipid matrices show neither a protection from aqueous environment, nor retardation capacities, nor a sufficient incorporation rate. Instead of the postulated inner oil droplets (NLC) or incorporated drug molecules (SLN) in the solid spherical matrix, drug or oil molecules, respectively, presented on the surface of solid lipid platelets were observed. Incorporation of drug or oil inside a crystallized matrix of a nanoparticle is not probable because crystals with their regular structures only tolerate rare defects to incorporate host molecules: Even lipophilic drug or oil, respectively, are ejected from the molten lipid mix during the lipid crystallization process at the cooling step. Conventional nanoemulsions surpass SLN and NLC in key parameters as drug load and protection of sensitive molecules! |