| Summary: | This research includes production of chitosan nanocapsules through ionic gelation with sodium bisulfate for nanoencapsulation of hydroxytyrosol (HT) using ultrasonication in tandem. The resulting nanocapsules encapsulating HT were analyzed for particle size, ζ-potential, packaging characteristics, FESEM, ATR-FTIR, XRD, DSC, in vitro release, antioxidant potential and antiproliferative properties. The nanocapsules (size 119.50–365.21 nm) were spherical to irregular shaped with positive ζ-potential (17.50–18.09 mV). The encapsulation efficiency of 5 mg/g HT (HTS1) and 20 mg/g HT (HTS2) was 77.13% and 56.30%, respectively. The nanocapsules were amorphous in nature with 12.34% to 15.48% crystallinity and crystallite size between 20 nm and 27 nm. Formation of nanocapsules resulted in increasing the glass transition temperature. HTS2 delivered 67.12% HT (HTS1 58.89%) at the end of the simulated gastrointestinal digestion. The nanoencapsulated HT showed higher antioxidant and antiproliferative (against A549 and MDA-MB-231 cancer cell lines) properties than the free HT.
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