Hyaluronic Acid-Coated Nanoliposomes as Delivery Systems for Fisetin: Stability, Membrane Fluidity, and Bioavailability

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Abstract
Fisetin has shown numerous health benefits, whereas its food application is constrained by water insolubility, poor stability, and low bioaccessibility. This work investigated the potential of hyaluronic acid (HA)-coated nanoliposomes for the encapsulation and delivery of fisetin. It was observed that HA can adsorb onto the liposomal membrane through hydrogen bonding and maintain the spherical shape of nanoliposomes. Fluorescence analysis suggested that the HA coating restricted the motion and freedom of phospholipid molecules in the headgroup region and reduced the interior micropolarity of the nanoliposomes but did not affect the fluidity of the hydrophobic core. These effects were more pronounced for the HA with a low molecular weight (35 kDa) and moderate concentration (0.4%). The HA coating improved the storage and thermal stability of the nanoliposomes, as well as the digestive stability and bioaccessibility of the encapsulated fisetin. These findings could guide the development of HA-coated nanoliposomes for the controlled delivery of hydrophobic bioactives such as fisetin in functional foods.

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