Tier 3 — preclinical

Nanoemulsion formulation of fisetin improves bioavailability and antitumour activity in mice

Ragelle H, Crauste-Manciet S, Seguin J, Brossard D, Scherman D, Arnaud P, Chabot GG
International Journal of Pharmaceutics 2012 427(2):452-9

Bibliography

PubMed
PMID 22387278
DOI
10.1016/j.ijpharm.2012.02.025
Funding
Not explicitly stated in the reviewed sections; conducted at Paris Descartes University, Faculty of Pharmacy, INSERM U1022, CNRS UMR8151, Chimie ParisTech, Paris.
Competing interests
Not stated in the reviewed sections.

Study snapshot

DesignDevelopment and physicochemical characterisation of a fisetin nanoemulsion (Miglyol 812N/Labrasol/Tween 80/Lipoid E80/water), followed by pharmacokinetic comparison of nanoemulsion vs. free fisetin after intravenous and intraperitoneal dosing in mice, and antitumour activity comparison in Lewis lung carcinoma-bearing mice.
ModelMice (pharmacokinetics) and Lewis lung carcinoma (LLC)-bearing mice (antitumour efficacy).
SampleStandard mouse pharmacokinetic and tumour-growth cohort sizes; exact n not stated in the reviewed sections.
InterventionFisetin nanoemulsion 13 mg/kg intravenous (pharmacokinetics); fisetin nanoemulsion 18.3 or 36.6 mg/kg vs. free fisetin 223 mg/kg (antitumour efficacy, intraperitoneal, repeated dosing).
DurationPharmacokinetics sampled over several hours post-dose; antitumour study followed tumour volume over approximately 18-20 days.
EndpointsNanoemulsion droplet size, zeta potential, polydispersity index, and 30-day stability; Plasma fisetin concentration-time profile (IV and IP dosing) and relative bioavailability; Lewis lung carcinoma tumour volume over time

What the study showed, in plain terms

Fisetin's poor water solubility limits how much of an oral or injected dose actually reaches the bloodstream, so this study built a nanoemulsion — tiny oil droplets carrying the drug — to see if that would help.

French researchers formulated fisetin into a stable nanoemulsion (about 153 nm droplets) and compared it with free fisetin for absorption and anticancer effect in mice with Lewis lung carcinoma tumours.

Injected directly into a vein, the nanoemulsion made no difference to how much fisetin reached the bloodstream compared with free fisetin. But given intraperitoneally — a route more like an oral dose in terms of absorption barriers — the nanoemulsion produced a 24-fold increase in fisetin's relative bioavailability, and slowed tumour growth at a much lower dose (36.6 mg/kg) than was needed with free fisetin (223 mg/kg).

Bottom line: a formulation-science result showing that packaging fisetin in a nanoemulsion can substantially improve how much of it the body actually absorbs when given by a route other than directly into a vein — relevant background for any product review discussing why fisetin supplements use specific delivery formats (e.g., liposomal or hydrogel formulations) to improve absorption.

Key findings

A fisetin nanoemulsion (153 nm droplets, stable 30 days at 4°C) showed no difference in systemic exposure versus free fisetin after intravenous dosing, but a 24-fold increase in relative bioavailability after intraperitoneal dosing; the nanoemulsion also achieved equivalent antitumour activity at a roughly 6-fold lower dose (36.6 mg/kg vs. 223 mg/kg) in Lewis lung carcinoma-bearing mice.

What this study can and cannot tell us

Mouse data only, using intravenous and intraperitoneal routes rather than oral administration, which is how fisetin supplements are actually consumed — so the bioavailability findings cannot be directly extrapolated to oral products. The nanoemulsion was unstable at 20°C, requiring refrigerated storage, which is a practical formulation limitation.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology