Elimination study of intact lipid nanocapsules after intravenous rat administration

Abstract

Aim: The present study investigated renal elimination after intravenous administration of four different formulations of lipid nanocapsules (LNCs) containing dyes adapted to Förster resonance energy transfer (FRET-LNCs). Materials & methods: FRET-LNCs of 85 or 50 nm with or without a pegylated surface were injected and collected in the blood or urine of rats at different time points. Quantitative analysis was performed to measure intact FRET-LNCs. Results & conclusion: No intact LNCs were found in urine (0 particles/ml) for all formulations. The 50-nm pegylated LNCs were eliminated faster from the blood, whereas 85-nm pegylated LNCS were eliminated slower than nonpegylated LNCs. Elimination of FRET-LNCs was mainly due to liver tissue interaction and not renal elimination.

TWEETABLE ABSTRACT

This study confirmed that the elimination of FRET LNCs is likely mainly due to liver tissue interaction and not renal elimination. #nanomedicines #lipidnanocapsules #FRET #pharmacokinetic #biodistribution

Summary points

• An in vivo rat pharmacokinetic study after intravenous administration of lipid nanocapsules was performed.

• Two types of formulations differing by size and surface were studied.

• Renal elimination of intact lipid nanocapsules was sought using the fluorescence resonance and energy transfer (FRET) technique.

• The FRET technique was also used to quantify intact nanoparticles in blood and urine.

• No intact nanoparticles were found in the urine after intravenous injection.

• The elimination mechanisms of the nanoparticles were shown to be hepatic and not renal.

Keywords: :

• drug delivery
• FRET
• lipid nanocapsules
• pharmacokinetics
• renal elimination

Author contributions

V Lebreton: conceptualization, investigation, methodology, data processing, visualization, investigation, writing the original draft. S Legeay: methodology, data processing, visualization. C Rapenne: investigation, data processing. P Saulnier: supervision, validation, reviewing. F Lagarce: supervision, validation, writing, reviewing.

Financial disclosure

This work was supported by Ligue contre le cancer Maine et Loire et Loiret Committee (JPB/FP-441/12.2019 NANOPK PROJECT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Protocol on animals was designed according to the EU Directive 2010/63/EU and was approved by the Committee on the Ethics of Animal Experiment of the Pays de la Loire, France (APAFIS #2020092411444021).

Additional information

Funding

This work was supported by Ligue contre le cancer Maine et Loire et Loiret Committee (JPB/FP-441/12.2019 NANOPK PROJECT).