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Here, HES-loaded liposomes were incorporated into a sodium alginate\/gelatin (SA\/G) composite hydrogel to construct a liposome-in-hydrogel delivery system. The SA\/G ratio was systematically optimized to establish a balanced polymer network through the complementary functions of SA and gelatin. The optimized formulation (H5) exhibited a compact three-dimensional network with cooperative intermolecular interactions, favorable thermal behavior and improved colloidal stability. During simulated gastrointestinal digestion, H5 suppressed premature HES release under oral and gastric conditions while promoting sustained intestinal release. H5 achieved a bioaccessibility of 26.80%, compared with 21.26% for liposomes and 14.26% for free HES, and showed approximately 23-fold and 5-fold higher intestinal tissue-associated accumulation, respectively. These findings indicate that rational optimization of the SA\/G network balances matrix integrity, hydration, and liposome stabilization, providing a promising food-grade strategy for controlled gastrointestinal delivery of poorly soluble bioactive compounds.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c08942","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:50Z","timestamp":1790834510000},"page":"31870-31884","source":"Crossref","is-referenced-by-count":0,"title":["Optimizing the Sodium Alginate\/Gelatin Ratio Enhances\nthe Stability and Intestinal Delivery of Hesperidin-Loaded Liposomes"],"prefix":"10.1021","volume":"74","author":[{"given":"Yexuan","family":"Yao","sequence":"first","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfeng","family":"Fang","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihang","family":"Hou","sequence":"additional","affiliation":[{"name":"Wuhan University , , ,","place":["Wuhan, China, 430072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Jiangxi Normal University , , ,","place":["Nanchang, China, 330022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5650-1507","authenticated-orcid":true,"given":"Zeyuan","family":"Deng","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]},{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3394-7861","authenticated-orcid":true,"given":"Ting","family":"Luo","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]},{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330200"]},{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2026101408092063100_cit1","doi-asserted-by":"publisher","first-page":"139505","DOI":"10.1016\/j.foodchem.2024.139505","article-title":"Facile construction\nof pectin-based hesperidin microcapsules: solubilization, stability,\nloading process, and release mechanism","volume":"451","author":"Zhou","year":"2024","journal-title":"Food\nChem."},{"key":"2026101408092063100_cit2","doi-asserted-by":"publisher","first-page":"147403","DOI":"10.1016\/j.foodchem.2025.147403","article-title":"Enhanced bioaccessibility of a hesperidin-rich\nblood orange extract after encapsulation in alginate\/chitosan microcapsules","volume":"499","author":"de Marco","year":"2026","journal-title":"Food Chem."},{"key":"2026101408092063100_cit3","doi-asserted-by":"publisher","first-page":"109872","DOI":"10.1016\/j.foodhyd.2024.109872","article-title":"Double-coated\nnanoliposomes improve the bioavailability of flavanone hesperetin","volume":"151","author":"Meng","year":"2024","journal-title":"Food Hydrocolloids"},{"key":"2026101408092063100_cit4","doi-asserted-by":"publisher","first-page":"135685","DOI":"10.1016\/j.foodchem.2023.135685","article-title":"Use of sodium\nalginate coatings to improve bioavailability\nof liposomes containing dpp-iv inhibitory collagen peptides","volume":"414","author":"Wu","year":"2023","journal-title":"Food Chem."},{"key":"2026101408092063100_cit5","doi-asserted-by":"publisher","first-page":"105743","DOI":"10.1016\/j.foodhyd.2020.105743","article-title":"Preparation,\nformation mechanism and in vitro dynamic digestion behavior of quercetin-loaded\nliposomes in hydrogels","volume":"104","author":"Liu","year":"2020","journal-title":"Food Hydrocolloids"},{"issue":"7","key":"2026101408092063100_cit6","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202514611","article-title":"Lipogels:\nrobust\nself-lubricating physically cross-linked alginate hydrogels embedded\nwith liposomes","volume":"36","author":"Ma","year":"2026","journal-title":"Adv. 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Biol. Macromol."},{"key":"2026101408092063100_cit29","doi-asserted-by":"publisher","first-page":"109606","DOI":"10.1016\/j.foodhyd.2023.109606","article-title":"Layer-by-layer self-assembled\nliposomes prepared using sodium alginate and chitosan : insights into\nvesicle characteristics and physicochemical stability","volume":"149","author":"Tan","year":"2024","journal-title":"Food Hydrocolloids"},{"issue":"18","key":"2026101408092063100_cit30","doi-asserted-by":"publisher","first-page":"16922","DOI":"10.1021\/acsami.9b02529","article-title":"Fabrication and characterization\nof layer-by-layer composite nanoparticles based on zein and hyaluronic\nacid for codelivery of curcumin and quercetagetin","volume":"11","author":"Chen","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2026101408092063100_cit31","doi-asserted-by":"publisher","first-page":"144240","DOI":"10.1016\/j.foodchem.2025.144240","article-title":"Sodium alginate\nhydrogel beads loaded with clove essential oil liposomes: preparation,\ncharacterization and fumigant activity","volume":"483","author":"Hu","year":"2025","journal-title":"Food\nChem."},{"key":"2026101408092063100_cit32","doi-asserted-by":"publisher","first-page":"108966","DOI":"10.1016\/j.foodres.2019.108966","article-title":"The influence\nof sodium alginate and genipin on physico-chemical\nproperties and stability of wpi coated liposomes","volume":"130","author":"Ghaleshahi","year":"2020","journal-title":"Food Res. Int."},{"key":"2026101408092063100_cit33","doi-asserted-by":"publisher","first-page":"106214","DOI":"10.1016\/j.foodhyd.2020.106214","article-title":"Fabrication\nand characterization\nof curcumin-loaded pea protein isolate-surfactant complexes at neutral\nph","volume":"111","author":"Guo","year":"2021","journal-title":"Food Hydrocolloids"},{"key":"2026101408092063100_cit34","doi-asserted-by":"publisher","first-page":"109268","DOI":"10.1016\/j.foodhyd.2023.109268","article-title":"Interaction\nof curcumin with four types of gelatins in nanoparticles:\nmechanism and application for emulsion stabilization","volume":"146","author":"Kan","year":"2024","journal-title":"Food Hydrocolloids"},{"key":"2026101408092063100_cit35","doi-asserted-by":"publisher","first-page":"107517","DOI":"10.1016\/j.foodhyd.2022.107517","article-title":"Two colorimetric\nfilms based on chitin whiskers and sodium alginate\/gelatin incorporated\nwith anthocyanins for monitoring food freshness","volume":"127","author":"Zheng","year":"2022","journal-title":"Food Hydrocolloids"},{"key":"2026101408092063100_cit36","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.foodchem.2016.01.052","article-title":"Physicochemical\nstability, microrheological properties and microstructure of lutein\nemulsions stabilized by multilayer membranes consisting of whey protein\nisolate, flaxseed gum and chitosan","volume":"202","author":"Xu","year":"2016","journal-title":"Food Chem."},{"key":"2026101408092063100_cit37","doi-asserted-by":"publisher","first-page":"106265","DOI":"10.1016\/j.foodhyd.2020.106265","article-title":"Formulated protein-polysaccharide-surfactant\nternary complexes for\nco-encapsulation of curcumin and resveratrol: characterization, stability\nand in vitro digestibility","volume":"111","author":"Guo","year":"2021","journal-title":"Food Hydrocolloids"},{"issue":"5","key":"2026101408092063100_cit38","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1021\/acs.jafc.0c06409","article-title":"Stability, interfacial\nstructure, and gastrointestinal digestion of \u03b2-carotene-loaded\npickering emulsions co-stabilized by particles, a biopolymer, and\na surfactant","volume":"69","author":"Wei","year":"2021","journal-title":"J. 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Food Chem."},{"issue":"13","key":"2026101408092063100_cit39","doi-asserted-by":"publisher","first-page":"2647","DOI":"10.3390\/nu14132647","article-title":"Bioavailability\nof hesperidin and its aglycone hesperetin-compounds\nfound in citrus fruits as a parameter conditioning the pro-health\npotential (neuroprotective and antidiabetic activity)-mini-review","volume":"14","author":"Wdowiak","year":"2022","journal-title":"Nutrients"},{"issue":"12","key":"2026101408092063100_cit40","doi-asserted-by":"publisher","first-page":"691","DOI":"10.31083\/ph.2016.6105","article-title":"Curcumin diethyl\ndisuccinate encapsulated in chitosan\/alginate nanoparticles for improvement\nof its in vitro cytotoxicity against mda-mb-231 human breast cancer\ncells","volume":"71","author":"Bhunchu","year":"2016","journal-title":"Pharmazie"}],"container-title":["Journal of Agricultural and Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c08942","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/40\/31870\/68722001\/acs.jafc.6c08942.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/40\/31870\/68722001\/acs.jafc.6c08942.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:26:20Z","timestamp":1791980780000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/40\/31870\/5443124\/Optimizing-the-Sodium-Alginate-Gelatin-Ratio"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":40,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2026,10,1]]},"published-print":{"date-parts":[[2026,10,14]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c08942","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}