{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:24:47Z","timestamp":1789680287356,"version":"4.0.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Cannabidiol (CBD) has a variety of pharmacological effects including antiepileptic, antispasmodic, anxiolytic and anti-inflammatory among other pharmacological effects. However, since CBD is a terpene-phenolic compound, its clinical application is limited by its poor water solubility, low stability, and low bioavailability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we used several strategies to address the above problems. Hydrochloric acid was used to modify zein to improve the molecular flexibility. Flexible zein nanoparticles (FZP-CBD) loaded with CBD was prepared to improve the stability and bioavailability of CBD. The parameters were evaluated in terms of morphology, particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), loading capacity (LC%), and storage stability. Simulated gastrointestinal fluid release experiment and bioavailability assay were applied in the evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The simulated gastrointestinal fluid experiment showed that the release rates of FZP-CBD and natural zein nanoparticles (NZP-CBD) loaded with CBD were 3.57% and 89.88%, respectively, after digestion with gastric fluid for 2 h, 92.12% and 92.56%, respectively, after intestinal fluid digestion for 2 h. Compared with NZP-CBD, the <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> of FZP-CBD at 3 different doses of CBD was increased by 1.7, 1.3 and 1.5 times respectively, and AUC<jats:sub>0-t<\/jats:sub> was increased by 1.4, 1.1 and 1.7 times respectively, bioavailability (F) was increased by 135.9%, 114.9%, 169.6% respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The experimental results showed that FZP-CBD could protect most of the CBD from being released in the stomach, and then control its release in the intestines, promote the absorption of CBD in the small intestine, and increase the bioavailability of CBD. Therefore, FZP-CBD could improve the utilization value of CBD and provide a new idea for the application of CBD in medicine and pharmacy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2024.1431620","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T12:26:37Z","timestamp":1721219197000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Enhanced oral bioavailability of cannabidiol by flexible zein nanoparticles: in vitro and pharmacokinetic studies"],"prefix":"10.3389","volume":"11","author":[{"given":"YingLan","family":"Nie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3389\/fphar.2020.00124","article-title":"From Cannabis sativa to Cannabidiol: promising therapeutic candidate for the treatment of neurodegenerative diseases","volume":"11","author":"Cassano","year":"2020","journal-title":"Front Pharmacol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3389\/fnbeh.2020.00109","article-title":"The pro-neurogenic effects of Cannabidiol and its potential therapeutic implications in psychiatric disorders","volume":"14","author":"Lujan","year":"2020","journal-title":"Front Behav Neurosci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"116070","DOI":"10.1016\/j.molliq.2021.116070","article-title":"Inclusion complexes of cannabidiol with \u03b2-cyclodextrin and its derivative: physicochemical properties, water solubility, and antioxidant activity","volume":"334","author":"Li","year":"2021","journal-title":"J Mol Liq"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1002\/ptr.6651","article-title":"Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults","volume":"34","author":"Hobbs","year":"2020","journal-title":"Phytother Res"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1177\/1060028018822124","article-title":"Epidiolex (Cannabidiol):A new Hope for patients with Dravet or Lennox-Gastaut syndromes","volume":"53","author":"Chen","year":"2019","journal-title":"Ann Pharmacother"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1586\/ern.11.27","article-title":"Sativex((R)) (tetrahydrocannabinol + cannabidiol), an endocannabinoid system modulator: basic features and main clinical data","volume":"11","author":"Vermersch","year":"2011","journal-title":"Expert Rev Neurother"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1021\/js9503338","article-title":"Absorption of Cam-2445, an NK1 neurokinin receptor antagonist: in vivo, in situ, and in vitro evaluations","volume":"85","author":"Helen Chan","year":"1996","journal-title":"J Pharm Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1111\/epi.14555","article-title":"Progress report on new antiepileptic drugs: a summary of the fourteenth Eilat conference on new antiepileptic drugs and devices (EILAT XIV). 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