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

Abstract

Fisetin (FST), a potent anticancer phytoconstituent, exhibits poor aqueous solubility and hence poor bioavailability. The aim of the present study is to improve the oral bioavailability of FST by encapsulating into PLGA NPs (poly-lactide-co-glycolic acid nanoparticles) as a complex of HPbCD (hydroxyl propyl beta cyclodextrin) and to assess its anti-cancer activity against breast cancer cells. FST-HPbCD inclusion complex (FHIC) was prepared and the supramolecular complex formation was characterized by FTIR, DSC, PXRD and 1 H NMR. FHIC encapsulated PLGA nanoparticles (FHIC-PNP) were prepared and were studied for in vitro anticancer activity, cellular uptake, apoptosis and reactive oxygen species generation in MCF-7 human breast cancer cells. Comparative bioavailability of FST was determined after oral administration in C57BL6 mice as pure FST and FHIC-PNP. The results revealed that FHIC-PNP not only enhanced the anti-cancer activity and apoptosis of FST against MCF-7 cells but also improved its oral bioavailability, as demonstrated by increased peak plasma concentration and total drug absorbed.

Curcumin and fisetin internalization into Saccharomyces cerevisiae cells via osmoporation: impact of multiple osmotic treatments on the process efficiency

“…Recent studies reported the use of microencapsulation for preparing fisetin formulations (Kadari et al . ). However, few studies report the use of S. cerevisiae cells for this purpose.…”

“…As previously commented, the addition of a third osmoporation stage under the conditions used in the present study adds, on average, 2 h and 30 min to the process, which may not be of interest as the gains are low. Recent studies reported the use of microencapsulation for preparing fisetin formulations (Kadari et al 2017). However, few studies report the use of S. cerevisiae cells for this purpose.…”

Anti‑cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In�vitro and in�vivo studies

“…The low solubility and low bioavailability of fisetin limit its further investigation. Previous studies have attempted to overcome these issues with the use of drug delivery vectors and improved preparation techniques ( 35 , 52 ), and it is expected that future studies will provide strategies for further clinical and translational research on fisetin.…”

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

“…Fisetin, a dietary flavonol, is known to improve glucose homeostasis and mitigates diabetic complications [43]. Several nanoformulations, such as fisetin-PLGA-hyroxypropyl β-cyclodextrin nanoparticles, fisetin-assembled solid lipid nanoparticles, and fisetin-loaded nanoemulsion, were reported to improve oral bioavailability and gastrointestinal stability of fisetin [165,315,316]. Fisetin-PCL-PLGA-PEG-COOH nanoparticles have been claimed to be an attractive formulation with an improved pharmacokinetic profile for efficient management of hyperglycaemia and oxidative stress [317].…”