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Lipid nanocapsules are treasured nanoparticulate systems, although they lack detectability in biological environments. To overcome this, we designed LNCs loaded simultaneously with fluorescent dye and superparamagnetic iron oxide nanoparticles (Dual LNCs). The introduction of both labels did not alter nanoparticle characteristics such as size (50 nm), size distribution (polydispersity index < 0.1) or surface modifications, including the effectiveness of targeting ligands. Furthermore, the colloidal stability, particle integrity and biocompatibility of the nanoparticles were not negatively affected by label incorporation. These Dual LNCs are concomitantly visualizable via fluorescence and transmitted light imaging after either the internalization by cells or systemic administration to mice. Importantly, they are detectable in liver sections of mice using transmission electron microscopy without additional enhancement. The iron content of 0.24% (m/m) is sufficiently high for precise quantification of nanoparticle concentrations via inductively coupled plasma optical emission spectroscopy. Dual LNCs are precious tools for the investigation of in vitro and in vivo performances of lipid nanocapsule formulations, since they allow for the use of complementary imaging methods for broad range detectability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lipid nanocapsules (LNCs) are extensively used as drug carrier systems, due to their small size distribution, biocompatibility and ease of preparation. They are especially useful for lipophilic drugs to overcome physicochemical constraints that limit their efficacy, such as low solubility in aqueous media. The aim of this work was to investigate the relationship between the intracellular availability of poorly soluble drugs delivered via LNCs and their biological efficacy in cells in vitro. Cyclosporin A (CsA) with a logP Oct = 4.3 (Lucangioli et al., 2003) and Itraconazole (It) with a logP Oct = 6.2 (Bhardwaj et al., 2013) served as model lipophilic compounds, as they are highly promising candidates for the treatment of neovascular ocular diseases. Due to their lipophilic properties and the resulting preference for the oily core of LNCs, high encapsulation efficiencies were achieved. Drug-loaded LNCs with particle sizes around 50 nm were grafted with an αvβ3 integrin ligand (RGD) to optimize cellular uptake by human dermal microvascular endothelial cells. Even though RGD-LNCs showed excellent internalization, they exhibited insufficient inhibitory effects in vitro regarding endothelial cell proliferation, vascular endothelial growth factor expression, and tube formation in contrast to free drugs. This loss of efficacy could be explained by negligible intracellular availability of the poorly soluble drugs from LNCs. [ABSTRACT FROM AUTHOR]