Specific quantification of intact lipid nanocapsules in rats using FRET: biodistribution and PBPK model development

AIMS: One major challenge is to quantify intact nanoparticles specifically to understand the pharmacokinetics (PK) of nanomedicines. Lipid nanocapsules (LNC) carrying Förster resonance energy transfer (FRET) trackers have been previously developed, and a quantification method has been applied in blood samples. MATERIALS & METHOD: A quantification method in liver, spleen, and lungs was developed, and the biodistribution of intact FRET-LNC of 50 nm (FRET-LNC-50) in rats after intravenous injection was performed. RESULTS: FRET-LNC-50 were extracted from organs using a newly developed extraction method, allowing their integrity preservation and quantification. This method allowed the assessment of the biodistribution study of intact LNC. A non-compartmental PK analysis was performed to calculate PK parameters. The most exposed organ was the liver, with a longer half-life than blood and other organs. The availability of specific biodistribution data allowed the development of the first physiologically based PK (PBPK) model, which represents an ideal platform to further aggregate biodistribution data from various nanoparticle types and to bring insight into PK mechanisms and structure-properties relationships of nanoparticles. CONCLUSION: This study presents the first biodistribution analysis of intact LNC using a validated quantification method, enabling the development of a PBPK model that improves the understanding of nanoparticle PK mechanisms.