Hesperidin and hesperetin are two important plant flavanones abundantly found in citrus fruit. They have discovered many biological activities to treat diseases, including cancer, diabetes, and Alzheimer's disease. Despite their various benefits, they have poor solubility, which reduces their bioavailability and absorption. In this study, nanophytosomes have been utilized to improve their payload's solubility and bioavailability. In the current study, hesperetin or hesperidin was complexed with Phospholipon 90G with a 2:1 or 3:1 molar ratio, respectively. The formation of associations between active compounds and phospholipid were confirmed by X‐ray diffraction (XRD), Fourier‐transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR) techniques. Dynamic light scattering data show that the prepared associations in the presence of body fluids can make nanoparticles in the range of 200–250 nm. In addition, oral administration demonstrated that Cmax of hesperidin and hesperetin was increased (up to four times) after complexation with the lipid. It is concluded that phospholipid association may be used as a suitable and straightforward strategy to improve therapeutic activities of hesperidin and hesperetin by increasing their solubility and bioavailability.

There is a growing interest in bioactive compounds particularly polyphenols as dietary sources, food ingredients with several putative beneficial activities such as antioxidant and antimicrobial properties. Understanding the underlying mechanisms of plant‐derived phenolic compounds can substantially help develop solutions and technologies to better control and alleviate oxidative stress, inflammation, and consequently cancer. Studies have indicated that the loading of natural phytoconstituents into appropriate nanoparticles can develop and broaden biological applications. There is a wide range of applications derived from nanotechnology and nanomedicine through developing the packaging, preservation, and bioavailability of natural phytochemical. The present paper provides an overview and highlight on the importance and potential of natural polyphenols particularly in food and pharmaceutical industries. Furthermore, nanotechnology approaches, bioavailability, and potential adverse effects are also discussed.