{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T04:47:16Z","timestamp":1785646036037,"version":"3.56.0"},"reference-count":23,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2016YFD0501310"],"award-info":[{"award-number":["2016YFD0501310"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Resveratrol (RES) is a natural polyphenolic compound characterized by poor aqueous solubility and significant first-pass metabolism, resulting in extremely low oral bioavailability. Although resveratrol-loaded nanostructured lipid carriers (RES-NLCs) have shown potential in enhancing oral absorption, direct experimental evidence for their intestinal lymphatic transport mechanism remains limited, and existing explanations is largely based on indirect inference. RES-NLCs were prepared, and their pharmacokinetics and lymphatic transport characteristics were evaluated using a laboratory-established mesenteric lymph duct\u2013jugular vein assisted reflux model in rats. Simultaneously, a 28-day repeated-dose toxicity study was conducted in ICR mice. Pharmacokinetic results showed that compared with RES-Sol, RES-NLCs increased Cmax by approximately 2.3-fold, improved relative bioavailability by 7-fold, and achieved an absolute bioavailability of 176%. The lymphatic transport model confirmed that RES-NLCs are absorbed via the intestinal lymphatic pathway. In the 28-day repeated-dose toxicity study, no mortality or obvious clinical symptoms were observed at a dose of 10 mg\/kg. The RES-NLCs group exhibited increased liver coefficient and decreased spleen coefficient. Hematological analysis showed a mild increase in red blood cell count, along with decreases in mean corpuscular volume and red blood cell distribution width coefficient of variation. Serum biochemistry revealed significant elevations in aspartate aminotransferase and alanine aminotransferase (p = 9 \u00d7 10\u22125 and p = 4.02 \u00d7 10\u22127, respectively). However, no significant differences were observed in the organ coefficients of the heart, lungs, kidneys, or brain. Body composition and magnetic resonance imaging showed no abnormalities, and histopathological examination of major organs including the liver, stomach, and intestines revealed no structural damage. These findings provide direct evidence that RES-NLCs enhance the oral bioavailability by promoting intestinal lymphatic uptake, suggesting that this system may serve as an effective delivery platform for poorly soluble hydrophobic drugs.<\/jats:p>","DOI":"10.3390\/ani16152337","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:20:18Z","timestamp":1785486018000},"page":"2337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lymph-Targeted Resveratrol-NLCs Improve Oral Bioavailability: Validation via Rat Mesenteric Lymph Collection System and In Vivo Safety"],"prefix":"10.3390","volume":"16","author":[{"given":"Xiaorui","family":"Zhang","sequence":"first","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"},{"name":"Core Facility of Molecular Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3028-8525","authenticated-orcid":false,"given":"Wenli","family":"Shi","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlin","family":"Yang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Lin","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Deng","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daojin","family":"Yu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaizhen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Core Facility of Molecular Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Basiouni, S., Tellez-Isaias, G., Latorre, J.D., Graham, B.D., Petrone-Garcia, V.M., El-Seedi, H.R., Yal\u00e7\u0131n, S., El-Wahab, A.A., Visscher, C., and May-Simera, H.L. 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