{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:15:41Z","timestamp":1791497741577,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Xanthohumol (XN), a prenylated chalcone isolated from Humulus lupulus L., exhibits a wide range of biological activities, including antioxidant, anti-inflammatory, and chemopreventive effects. However, its therapeutic application is limited by poor aqueous solubility, low chemical stability, and rapid clearance from the systemic circulation. The present study aimed to develop and characterize a novel nano-sized drug-delivery system for XN that combines favourable colloidal stability, efficient encapsulation, sustained release, and reduced recognition by macrophages (\u201cstealth-like\u201d properties). To achieve this, XN-loaded cationic liposomes were coated with two marine polysaccharides, iota-carrageenan (CAR) and fucoidan (FUC), followed by Ca2+-mediated cross-linking. Liposomes were prepared by the ethanol injection method, and formulation parameters were optimized using a 23 + 1 full factorial design. Surface modification and cross-linking conditions were further optimized through polyelectrolyte titration and a Taguchi L9 orthogonal array. The resulting nanocarriers were evaluated for particle size, polydispersity, \u03b6-potential, encapsulation efficiency, release behavior, and cellular uptake. Both coatings significantly prolonged XN release compared with uncoated liposomes, with CAR-coated vesicles providing the most sustained release (\u224855% over 48 h). In RAW264.7 macrophages, 50 \u00b5g\/mL CAR-coated liposomes reduced cellular uptake by approximately 74% following 1-h incubation relative to uncoated controls and maintained this reduction over 2 h whereas FUC-coated vesicles afforded only transient early evasion. The cross-linked iota-carrageenan coating thus represents a promising strategy for conferring stable \u201cstealth-like\u201d characteristics to XN-loaded liposomes intended for prolonged drug delivery.<\/jats:p>","DOI":"10.3390\/polym18141724","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:55:21Z","timestamp":1783990521000},"page":"1724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biopolymer Surface Modification as a Strategy for Conferring \u201cStealth-like\u201d Characteristics of Xanthohumol-Loaded Liposomes"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2333-9879","authenticated-orcid":false,"given":"Plamen","family":"Simeonov","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute at Medical University of Plovdiv (RIMU), 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9840-6890","authenticated-orcid":false,"given":"Velislava","family":"Todorova","sequence":"additional","affiliation":[{"name":"Research Institute at Medical University of Plovdiv (RIMU), 4002 Plovdiv, Bulgaria"},{"name":"Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-1945","authenticated-orcid":false,"given":"Tsvetelina","family":"Batsalova","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Faculty of Biology, Paisii Hilendarski University of Plovdiv, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8052-5840","authenticated-orcid":false,"given":"Balik","family":"Dzhambazov","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Faculty of Biology, Paisii Hilendarski University of Plovdiv, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1282-7868","authenticated-orcid":false,"given":"Stanislava","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Research Institute at Medical University of Plovdiv (RIMU), 4002 Plovdiv, Bulgaria"},{"name":"Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9158-6208","authenticated-orcid":false,"given":"Plamen","family":"Katsarov","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute at Medical University of Plovdiv (RIMU), 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"754","DOI":"10.3390\/molecules20010754","article-title":"Pharmacological Profile of Xanthohumol, a Prenylated Flavonoid from Hops (Humulus Lupulus)","volume":"20","author":"Liu","year":"2015","journal-title":"Molecules"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jiang, C.-H., Sun, T.-L., Xiang, D.-X., Wei, S.-S., and Li, W.-Q. 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