Tier 3 — preclinical

Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPβCD in polymeric nanoparticles

Kadari A, Gudem S, Kulhari H, Bhandi MM, Borkar RM, Kolapalli VRM, Sistla R
Drug Delivery 2017 24(1):224-32

Bibliography

PubMed
PMID 28156161
PubMed Central
PMC8241160
DOI
10.1080/10717544.2016.1245366
Funding
Not stated in the reviewed abstract/metadata; conducted at CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Competing interests
Not stated in the reviewed abstract/metadata.

Study snapshot

DesignDevelopment and characterisation of a fisetin-hydroxypropyl-beta-cyclodextrin (HPβCD) inclusion complex encapsulated in PLGA polymeric nanoparticles (FHIC-PNP), followed by in vitro anticancer activity, cellular uptake, apoptosis and reactive oxygen species assays in MCF-7 breast cancer cells, and comparative oral bioavailability of FHIC-PNP versus pure fisetin in C57BL/6 mice.
ModelMCF-7 human breast cancer cells (in vitro) and C57BL/6 mice (oral bioavailability, in vivo).
SampleStandard cell-culture replicate and mouse pharmacokinetic cohort sizes; exact n not stated in the reviewed abstract/metadata.
InterventionFisetin-HPβCD inclusion complex encapsulated in PLGA nanoparticles (FHIC-PNP) versus pure fisetin, tested for anticancer activity in MCF-7 cells and for oral bioavailability in mice.
DurationNot stated in the reviewed abstract/metadata.
EndpointsIn vitro anticancer activity, cellular uptake, apoptosis and reactive oxygen species generation in MCF-7 cells; Oral bioavailability in mice (peak plasma concentration and total drug absorbed) versus pure fisetin

What the study showed, in plain terms

Fisetin is poorly absorbed when taken by mouth, so researchers looked for a way to package it that would help more of it reach the bloodstream.

A team in India built a nanoparticle formulation that first locks fisetin inside a cyclodextrin carrier (HPβCD) and then encapsulates that complex inside PLGA polymer nanoparticles, and tested it against plain fisetin in breast cancer cells and in mice.

In MCF-7 breast cancer cells, the nanoparticle formulation increased cellular uptake, apoptosis and reactive-oxygen-species generation compared with plain fisetin, and improved anticancer activity. Given orally to mice, it also produced a higher peak blood concentration and greater total drug absorbed than plain fisetin.

Bottom line: another formulation-science result showing that wrapping fisetin in a cyclodextrin-nanoparticle carrier can improve both its oral absorption and its cell-level anticancer activity compared with the unformulated compound — relevant background for why fisetin supplements use specialised delivery formats to improve absorption.

Key findings

A fisetin-HPβCD inclusion complex encapsulated in PLGA nanoparticles (FHIC-PNP) improved oral bioavailability in mice (higher peak plasma concentration and total drug absorbed) compared with pure fisetin, and enhanced anticancer activity, cellular uptake, apoptosis and reactive oxygen species generation in MCF-7 breast cancer cells.

What this study can and cannot tell us

Preclinical only — MCF-7 cell-line and mouse data, no human pharmacokinetic or clinical outcome data. Anticancer findings are specific to a breast cancer cell line and cannot be generalised to other indications or to healthy-ageing use cases.

Citation network

Articles citing this research paper

2 articles

Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

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