{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:05:46Z","timestamp":1789873546472,"version":"4.0.1"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013142","name":"Key Research and Development Project of Hainan Province","doi-asserted-by":"publisher","award":["ZDYF2024XDNY191"],"award-info":[{"award-number":["ZDYF2024XDNY191"]}],"id":[{"id":"10.13039\/501100013142","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013142","name":"Key Research and Development Project of Hainan Province","doi-asserted-by":"publisher","award":["ZDYF2026XDNY141"],"award-info":[{"award-number":["ZDYF2026XDNY141"]}],"id":[{"id":"10.13039\/501100013142","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32272240"],"award-info":[{"award-number":["32272240"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32272240"],"award-info":[{"award-number":["32272240"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Major Science and Technology Project of Haikou City","award":["2023-001"],"award-info":[{"award-number":["2023-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mar. Drugs","Marine Drugs"],"abstract":"<jats:p>Collagen peptides (CPs) possess diverse biological activities, yet their oral efficacy is limited by gastrointestinal degradation and restricted systemic exposure of intact bioactive peptide species. Herein, a stable cholesterol-free nanoliposome system was developed using soybean phospholipids and stigmasterol through high-pressure microfluidization, followed by tangential flow filtration and spray drying to obtain a stable dry formulation. The optimized nanoliposomes exhibited a particle size below 100 nm, high peptide loading, excellent redispersibility, and remarkable physicochemical stability during refrigerated storage and under different pH and thermal conditions. During simulated gastrointestinal digestion, the stigmasterol-stabilized phospholipid bilayer effectively preserved encapsulated CPs throughout the gastric phase while facilitating peptide release under intestinal conditions. Oral administration in rats significantly enhanced collagen peptide bioavailability, increasing the plasma exposure (iAUC0\u20138 h) of total hydroxyproline by 3.84-fold compared with free CPs. Peptide-bound hydroxyproline exposure increased 9.3-fold and accounted for approximately 94% of total absorbed hydroxyproline. UHPLC\u2013HRMS analysis confirmed substantially enhanced systemic exposure of multiple characteristic hydroxyproline-containing dipeptides and tripeptides following nanoliposomal delivery. These findings indicate that stigmasterol-containing nanoliposomes improve the gastrointestinal stability and systemic delivery performance of collagen peptides, providing a promising strategy for enhancing the oral delivery potential of food-derived bioactive peptides.<\/jats:p>","DOI":"10.3390\/md24080293","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:20:36Z","timestamp":1787322036000},"page":"293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stigmasterol-Stabilized Nanoliposomes Enhance Oral Delivery of Collagen Peptides Through Improved Systemic Exposure of Hydroxyproline-Containing Peptides"],"prefix":"10.3390","volume":"24","author":[{"given":"Zifang","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266000, China"},{"name":"Haikou Research & Development Center for Biopeptide Engineering, Huayan Collagen Technology Co., Ltd., Haikou 570100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-4021","authenticated-orcid":false,"given":"Wenshuo","family":"Xing","sequence":"additional","affiliation":[{"name":"Sanya Oceanographic Institution, Ocean University of China, Sanya 572024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meichao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Weihai Institute for Food and Drug Control, Weihai 264200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengsuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Sanya Oceanographic Institution, Ocean University of China, Sanya 572024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3852-2608","authenticated-orcid":false,"given":"Haohao","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266000, China"},{"name":"Sanya Oceanographic Institution, Ocean University of China, Sanya 572024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhu","family":"Xue","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jff.2014.09.010","article-title":"Porcine skin gelatin hydrolysate as a dipeptidyl peptidase IV inhibitor improves glycemic control in streptozotocin-induced diabetic rats","volume":"11","author":"Huang","year":"2014","journal-title":"J. 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