{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:41:06Z","timestamp":1788576066184,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T00:00:00Z","timestamp":1651881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"publisher","award":["31972730"],"award-info":[{"award-number":["31972730"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"publisher","award":["00109023"],"award-info":[{"award-number":["00109023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Agricultural University","award":["31972730"],"award-info":[{"award-number":["31972730"]}]},{"name":"China Agricultural University","award":["00109023"],"award-info":[{"award-number":["00109023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Curcumin is a natural acidic polyphenol extracted from turmeric with a wide range of biological and pharmacological effects. However, the application of curcumin for animal production and human life is limited by a low oral bioavailability. In this study, natural curcumin was prepared for the curcumin \u03b2-cyclodextrin inclusion complex (CUR-\u03b2-CD), curcumin solid dispersion (CUR-PEG-6000), and curcumin phospholipid complex (CUR-HSPC) using co-precipitation, melting, and solvent methods, respectively. Curcumin complex formations were monitored using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) techniques via the shifts in the microscopic structure, molecular structure, and crystalline state. Subsequently, twenty-four female beagle dogs were randomly divided into four groups to receive unmodified curcumin and three other curcumin preparations. The validated UPLC\u2013MS assay was successfully applied to pharmacokinetic and bioavailability studies of curcumin in beagle dog plasma, which were collected after dosing at 0 min (predose), 5 min, 15 min, 30 min, 40 min, 50 min, 1.5 h, 3 h, 4.5 h, 5.5 h, 6 h, 6.5 h, 9 h, and 24 h. The relative bioavailabilities of CUR-\u03b2-CD, CUR-PEG-6000, and CUR-HSPC were 231.94%, 272.37%, and 196.42%, respectively. This confirmed that CUR-\u03b2-CD, CUR-HSPC, and especially CUR-PEG-6000 could effectively improve the bioavailability of curcumin.<\/jats:p>","DOI":"10.3390\/molecules27092998","type":"journal-article","created":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T21:31:20Z","timestamp":1652045480000},"page":"2998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Comparative Study of Preparation, Evaluation, and Pharmacokinetics in Beagle Dogs of Curcumin \u03b2-Cyclodextrin Inclusion Complex, Curcumin Solid Dispersion, and Curcumin Phospholipid Complex"],"prefix":"10.3390","volume":"27","author":[{"given":"Wanrong","family":"Song","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xizhao","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Anheal Laboratories Co., Ltd., Beijing 100094, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4677-0524","authenticated-orcid":false,"given":"Chongshan","family":"Dai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Degui","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelin","family":"Pang","sequence":"additional","affiliation":[{"name":"Beijing Anheal Laboratories Co., Ltd., Beijing 100094, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1541-5180","authenticated-orcid":false,"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yipeng","family":"Jin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4422-2492","authenticated-orcid":false,"given":"Jiahao","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Center of Research and Innovation of Chinese Traditional Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tung, B.T., Dong, T.N., Hai, N.T., and Dang, K.T. (2019). Curcuma longa, the polyphenolic curcumin compound and pharmacological effects on liver. Diet. Interv. Liver Dis., 125\u2013134.","DOI":"10.1016\/B978-0-12-814466-4.00010-0"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/0976-9668.107253","article-title":"Role of curcumin in systemic and oral health: An overview","volume":"4","author":"Nagpal","year":"2013","journal-title":"J. Nat. Sci. Biol. M"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.joim.2022.02.008","article-title":"Effects of turmeric (curcuma longa) and its constituent (curcumin) on the metabolic syndrome: An updated review","volume":"20","author":"Vafaeipour","year":"2022","journal-title":"J. Integr. Med."},{"key":"ref_4","first-page":"1058","article-title":"Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin e2 production","volume":"61","author":"Jones","year":"2001","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1111\/j.1745-7254.2007.00651.x","article-title":"Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated bv2 microglia","volume":"28","author":"Jin","year":"2007","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/10408690490424702","article-title":"Biological properties of curcumin-cellular and molecular mechanisms of action","volume":"44","author":"Joe","year":"2004","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/164456a0","article-title":"Antibacterial action of curcumin and related compounds","volume":"164","author":"Bernt","year":"1949","journal-title":"Nature"},{"key":"ref_8","first-page":"2109","article-title":"Synergistic antibacterial activity of curcumin with antibiotics against staphylococcus aureus","volume":"28","author":"Teow","year":"2015","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.phymed.2013.02.006","article-title":"Synergistic antibacterial effect of curcumin against methicillin-resistant staphylococcus aureus","volume":"20","author":"Mun","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"18283","DOI":"10.3390\/molecules191118283","article-title":"Curcumin reverse methicillin resistance in staphylococcus aureus","volume":"19","author":"Kong","year":"2014","journal-title":"Molecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1177\/030089168707300105","article-title":"Turmeric and curcumin as topical agents in cancer therapy","volume":"73","author":"Kuttan","year":"1987","journal-title":"Tumori"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"152556","DOI":"10.1016\/j.prp.2019.152556","article-title":"Curcumin inhibits nf-kb and wnt\/\u03b2-catenin pathways in cervical cancer cells","volume":"215","author":"Ghasemi","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.nano.2014.09.004","article-title":"Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent","volume":"11","author":"Krausz","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1099\/vir.0.80424-0","article-title":"Characterization of an infectious cdna copy of the genome of a naturally occurring, avirulent coxsackievirus b3 clinical isolate","volume":"86","author":"Lee","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.otohns.2004.06.322","article-title":"Curcumin suppresses growth of head and neck squamous cell carcinoma","volume":"131","author":"Lotempio","year":"2004","journal-title":"Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.3109\/00016357.2013.769627","article-title":"Effectiveness of curcumin against enterococcus faecalis biofilm","volume":"71","author":"Neelakantan","year":"2013","journal-title":"Acta Odontol. Scand."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6252","DOI":"10.3748\/wjg.v23.i34.6252","article-title":"Curcumin inhibits hepatitis b virus infection by downregulating ccc dna-bound histone acetylation","volume":"23","author":"Wei","year":"2017","journal-title":"World J. Gastr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2000171","DOI":"10.1002\/cbdv.202000171","article-title":"Antibacterial mechanism of curcumin: A review","volume":"17","author":"Zheng","year":"2020","journal-title":"Chem. Biodivers."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1177\/0022034509356169","article-title":"Curcumin produces an antihyperalgesic effect via antagonism of trpv1","volume":"89","author":"Yeon","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_20","first-page":"161","article-title":"Safety and anti-inflammatory activity of curcumin: A component of tumeric (curcuma longa)","volume":"1","year":"2003","journal-title":"J. Altern. Complementary Med."},{"key":"ref_21","first-page":"69","article-title":"Study on toxicity of single and multiple dose curcumin in animals","volume":"35","author":"Cheng","year":"2019","journal-title":"Chin. J. Clin. Pharmacol."},{"key":"ref_22","unstructured":"Garcea, G. (2003). Bioavailability and Pharmacodynamics of Curcumin in Humans with Resectable Colorectal Primaries and Secondary Hepatic Metastases. [Master\u2019s Thesis, University of Leicester]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tifs.2015.10.015","article-title":"Emulsion-based encapsulation and delivery systems for polyphenols","volume":"47","author":"Lu","year":"2016","journal-title":"Trends Food Sci. Tech."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"793","DOI":"10.3390\/pharmaceutics3040793","article-title":"Encapsulation of natural polyphenolic compounds; A review","volume":"3","author":"Munin","year":"2011","journal-title":"Pharmaceutics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jff.2013.12.010","article-title":"Common delivery systems for enhancing in vivo bioavailability and biological efficacy of nutraceuticals","volume":"7","author":"Ting","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_26","first-page":"317","article-title":"Recent advances in research on preparation technologies and applications of tea polyphenol nanoparticles","volume":"32","author":"Luo","year":"2011","journal-title":"Food Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1124\/dmd.106.011460","article-title":"Peracetylation as a means of enhancing in vitro bioactivity and bioavailability of epigallocatechin-3-gallate","volume":"34","author":"Lambert","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.foodchem.2013.12.067","article-title":"Curcumin-\u03b2-cyclodextrin inclusion complex: Stability, solubility, characterisation by ft-ir, ft-raman, x-ray diffraction and photoacoustic spectroscopy, and food application","volume":"153","author":"Mangolim","year":"2014","journal-title":"Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.ejpb.2013.09.007","article-title":"Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs","volume":"85","author":"Vo","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_30","first-page":"193","article-title":"A review of the bioavailability and clinical efficacy of milk thistle phytosome: A silybin-phosphatidylcholine complex (siliphos)","volume":"10","author":"Kidd","year":"2005","journal-title":"Altern. Med. Rev. A J. Clin. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.3762\/bjoc.15.163","article-title":"Water inside \u03b2-cyclodextrin cavity: Amount, stability and mechanism of binding","volume":"15","author":"Pereva","year":"2019","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.crci.2010.04.003","article-title":"Cyclodextrins and their applications in aqueous-phase metal-catalyzed reactions","volume":"14","author":"Hapiot","year":"2011","journal-title":"Comptes Rendus Chim."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1021\/cg060001o","article-title":"Selective crystallization of the metastable form iv polymorph of tolbutamide in the presence of 2,6-di-o-methyl-\u03b2-cyclodextrin in aqueous solution","volume":"6","author":"Sonoda","year":"2006","journal-title":"Cryst. Growth Des."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ijpharm.2016.07.030","article-title":"Thirty years with cyclodextrins","volume":"514","author":"Bochot","year":"2016","journal-title":"Int. J. Pharmaceut."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1002\/jps.2600600902","article-title":"Pharmaceutical applications of solid dispersion systems","volume":"60","author":"Chiou","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_36","first-page":"1","article-title":"Complexes between phospholipids and vegetal derivatives of biological interest","volume":"60","author":"Bombardelli","year":"1989","journal-title":"Fitoterapia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.ajps.2018.05.011","article-title":"Phyto-phospholipid complexes (phytosomes): A novel strategy to improve the bioavailability of active constituents","volume":"14","author":"Lu","year":"2019","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_38","first-page":"629593","article-title":"In vitro and in vivo evaluation of oxatomide \u03b2-cyclodextrin inclusion complex","volume":"2013","author":"Hashem","year":"2013","journal-title":"J. Pharm."},{"key":"ref_39","first-page":"133","article-title":"Pharmacokinetics of curcumin self-microemulsions in beagle dogs","volume":"20","author":"Shi","year":"2014","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"key":"ref_40","first-page":"64","article-title":"Research progress on pharmacokinetics of three main components of turmeric","volume":"14","author":"Li","year":"2020","journal-title":"J. Dis. Monit. Control."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1208\/s12249-015-0337-6","article-title":"Microparticles containing curcumin solid dispersion: Stability, bioavailability and anti-inflammatory activity","volume":"17","author":"Teixeira","year":"2016","journal-title":"AAPS PharmSciTech"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10847-013-0322-1","article-title":"Comparison and correlation of in vitro, in vivo and in silico evaluations of alpha, beta and gamma cyclodextrin complexes of curcumin","volume":"78","author":"Patro","year":"2014","journal-title":"J. Incl. Phenom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1208\/s12249-011-9732-9","article-title":"Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion","volume":"13","author":"Wan","year":"2011","journal-title":"AAPS Pharmscitech"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ijpharm.2003.11.014","article-title":"Characterization of curcumin-pvp solid dispersion obtained by spray drying","volume":"271","author":"Paradkar","year":"2004","journal-title":"Int. J. Pharmaceut."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2165\/11319320-000000000-00000","article-title":"Multiple peaking phenomena in pharmacokinetic disposition","volume":"49","author":"Davies","year":"2010","journal-title":"Clin. Pharmacokinet."},{"key":"ref_46","first-page":"828","article-title":"Advances in studies on curcumin","volume":"40","author":"Yu","year":"2009","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00280-006-0355-x","article-title":"Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine","volume":"60","author":"Marczylo","year":"2007","journal-title":"Cancer Chemother. Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/jphp.12857","article-title":"Studies on the curcumin phospholipid complex solidified with soluplus\u00ae","volume":"70","author":"Wang","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.ccr.2008.08.011","article-title":"Inclusion complexation, encapsulation interaction and inclusion number in cyclodextrin chemistry","volume":"253","author":"Le","year":"2009","journal-title":"Coordin. Chem. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3109\/10717544.2013.853213","article-title":"Enhanced oral bioavailability of acyclovir by inclusion complex using hydroxypropyl-\u03b2-cyclodextrin","volume":"21","author":"Nair","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.tifs.2020.08.009","article-title":"Applications of cyclodextrins in food science. A review","volume":"104","author":"Matencio","year":"2020","journal-title":"Trends Food Sci. Tech."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0378-5173(01)00891-2","article-title":"The mechanisms of drug release from solid dispersions in water-soluble polymers","volume":"231","author":"Craig","year":"2002","journal-title":"Int. J. Pharmaceut."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jddst.2017.06.010","article-title":"Application of surfactants in solid dispersion technology for improving solubility of poorly water soluble drugs","volume":"41","author":"Chaudhari","year":"2017","journal-title":"J. Drug Deliv. Sci. Tec."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jff.2014.12.030","article-title":"Nanoemulsion-based delivery systems for nutraceuticals: Influence of carrier oil type on bioavailability of pterostilbene","volume":"13","author":"Sun","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jff.2015.02.044","article-title":"Enhancing nutraceutical bioavailability using excipient emulsions: Influence of lipid droplet size on solubility and bioaccessibility of powdered curcumin","volume":"15","author":"Zou","year":"2015","journal-title":"J. Funct. Foods"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/9\/2998\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:07:26Z","timestamp":1760137646000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/9\/2998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,7]]},"references-count":55,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["molecules27092998"],"URL":"https:\/\/doi.org\/10.3390\/molecules27092998","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,7]]}}}