The fantastic voyage of solid lipid nanoparticles from the lung to the brain: non‐invasive tomographic imaging as a feasible refinement process

Solid Lipid Nanoparticles (SLN) are colloidal drug delivery systems characterized by higher entrapment efficiency, good scalability of the preparation process and increased sustained release of the payload. Surface functionalization of SLN with ligands to achieve a site specific targeting makes them attractive to overcome the limited BloodBrain Barrier (BBB) penetration of therapeutic compounds. SLN are prepared for brain targeting by exploiting the adaptability of warm microemulsion process for the covalent surface modification with an Apolipoprotein Ederived peptide (SLNmApoE). Furthermore, the influence of the administration route on SLNmApoE brain bioavailability is here evaluated by means of Fluorescence Molecular Tomography, an advanced optical imaging technology that uses the NearInfrared Spectrum (NIR) (600–900 nm) for noninvasive in vivo imaging and ThreeDimensional (3D) quantification of the fluorescent probes. Fluorescent labelled SLNmApoE are able to cross intact a BBB in vitro model. The pulmonary administration of SLNmApoE is related to a higher confinement in the brain of Balb/c mice compared to the intravenous and intraperitoneal administration routes, without inducing any acute inflammatory reaction in the lungs. These results promote the pulmonary administration of braintargeted SLN as a feasible strategy for improving brain delivery of therapeutics as well as the FMT’s ability of quantitative assessment in vivobiodistribution studies.