{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:48:11Z","timestamp":1785422891827,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Institutes of T\u00fcrkiye","award":["33833"],"award-info":[{"award-number":["33833"]}]},{"award":["33833"],"award-info":[{"award-number":["33833"]}],"id":[{"id":"https:\/\/ror.org\/01d6ka036","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Hydrophobic deep eutectic solvents (HDESs) have been recognized as effective environmentally friendly extraction media for the recovery of lipophilic bioactive chemicals. Nonetheless, their incorporation with sophisticated delivery systems remains mostly unexamined. This study aimed to develop a curcuminoid-rich powder formulation from turmeric (Curcuma longa L.) and to evaluate its physicochemical properties, antioxidant activity, and effects on cell metabolic activity in vitro. Initially, 30 HDES systems based on thymol or menthol were prepared and compared in terms of their curcuminoid extraction performance. The thymol\/lactic acid system (2:1, molar ratio) produced the highest total curcuminoid concentration among the screened HDES systems. The extraction parameters were subsequently optimized using a Box\u2013Behnken response surface design. Under the optimized conditions, the total curcuminoid concentration in the analyzed extract solution was 6692.12 ppm. Then, the obtained extracts were incorporated into a double-layer emulsification system by high-pressure homogenization and converted into encapsulated powder form by spray-drying. The particle distribution index (PDI) of the prepared emulsion system was determined as 0.282, indicating a homogeneous distribution of particles within the emulsion system. The total curcuminoid-based encapsulation efficiency of turmeric powders obtained using a double-layer encapsulation system was determined to be 87.33%. Under separately simulated gastric and intestinal conditions, the detected curcuminoid recovery values were similar, at 31.24% and 31.10%, respectively. The ABTS radical-scavenging activity measured after the simulated intestinal treatment reached 81.57%. However, the possible contribution of residual HDES components to this activity could not be determined. The encapsulated powder caused a concentration-dependent reduction in the metabolic activity of DU-145 prostate cancer and Caco-2 colorectal adenocarcinoma cells in the MTT assay. To conclude, the integrated approach enabled the production of a curcuminoid-rich powder with high encapsulation efficiency. The findings support further investigation of the formulation\u2019s technological and biological properties.<\/jats:p>","DOI":"10.3390\/foods15152601","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:27Z","timestamp":1785131367000},"page":"2601","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydrophobic Deep Eutectic Solvent-Derived Curcuminoids Loaded into a Double-Layer Colloidal Delivery System: Physicochemical Properties and In Vitro Biological Activity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-8514","authenticated-orcid":false,"given":"\u0130rem","family":"Toprak\u00e7\u0131","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Istanbul University-Cerrahpa\u015fa, Istanbul 34320, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Torun","sequence":"additional","affiliation":[{"name":"Department of Food Engineering, Akdeniz University, Antalya 07070, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2241-2562","authenticated-orcid":false,"given":"Ebru","family":"Kurtulba\u015f","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Istanbul University-Cerrahpa\u015fa, Istanbul 34320, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0206-0117","authenticated-orcid":false,"given":"Mahmut","family":"Yildiztekin","sequence":"additional","affiliation":[{"name":"Department of Crop and Animal Production, Vocational School of K\u00f6yce\u011fiz, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9989-9823","authenticated-orcid":false,"given":"Selin","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Istanbul University-Cerrahpa\u015fa, Istanbul 34320, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Den Hartogh, D.J., Gabriel, A., and Tsiani, E. (2020). Antidiabetic Properties of Curcumin I: Evidence from In Vitro Studies. Nutrients, 12.","DOI":"10.3390\/nu12010118"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117037","DOI":"10.1016\/j.molliq.2021.117037","article-title":"Enhanced Solubility and Improved Stability of Curcumin in Novel Water-in-Deep Eutectic Solvent Microemulsions","volume":"339","author":"Dhingra","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14620","DOI":"10.33263\/BRIAC116.1462014633","article-title":"PH, Viscosity of Hydrophobic Based Natural Deep Eutectic Solvents and the Effect of Curcumin Solubility in It","volume":"11","author":"Sekharan","year":"2021","journal-title":"Biointerface Res. Appl. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/mnfr.201000310","article-title":"Exploring Solid Lipid Nanoparticles to Enhance the Oral Bioavailability of Curcumin","volume":"55","author":"Kakkar","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.foodhyd.2014.07.011","article-title":"Preparation and Characterization of Nanoemulsion Encapsulating Curcumin","volume":"43","author":"Sari","year":"2015","journal-title":"Food Hydrocoll."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e115121","DOI":"10.1590\/fst.115121","article-title":"Curcumin-Loaded Nano-Emulsion Prepared by High Pressure Homogenization: Impact of Emulsifiers on Physicochemical Stability and In Vitro Digestion","volume":"42","author":"Chen","year":"2022","journal-title":"Food Sci. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jfoodeng.2018.09.007","article-title":"Evaluating the Effect of Chitosan Layer on Bioaccessibility and Cellular Uptake of Curcumin Nanoemulsions","volume":"243","author":"Silva","year":"2019","journal-title":"J. Food Eng."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.lwt.2017.04.074","article-title":"Preparation of Curcumin-Loaded Emulsion Using High Pressure Homogenization: Impact of Oil Phase and Concentration on Physicochemical Stability","volume":"84","author":"Ma","year":"2017","journal-title":"LWT"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104384","DOI":"10.1016\/j.microc.2019.104384","article-title":"Hydrophobic Deep Eutectic Solvents in Microextraction Techniques\u2014A Review","volume":"152","year":"2020","journal-title":"Microchem. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7898","DOI":"10.1021\/acs.langmuir.2c00181","article-title":"pH-Responsive Regulation of a Surfactant-Free Microemulsion Based on Hydrophobic Deep Eutectic Solvents","volume":"38","author":"Jing","year":"2022","journal-title":"Langmuir"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"116950","DOI":"10.1016\/j.molliq.2021.116950","article-title":"Physicochemical Properties and Antibacterial Activity of Hydrophobic Deep Eutectic Solvent-in-Water Nanoemulsion","volume":"338","author":"Zeng","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17443","DOI":"10.1039\/D2RA01782B","article-title":"Therapeutic Hydrophobic Deep Eutectic Solvents of Menthol and Fatty Acid for Enhancing Anti-Inflammation Effects of Curcuminoids and Curcumin on RAW264.7 Murine Macrophage Cells","volume":"12","author":"Kongpol","year":"2022","journal-title":"RSC Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133728","DOI":"10.1016\/j.foodchem.2022.133728","article-title":"Extraction of Curcuminoids and Ar-Turmerone from Turmeric (Curcuma longa L.) Using Hydrophobic Deep Eutectic Solvents (HDESs) and Application as HDES-Based Microemulsions","volume":"396","author":"Kongpol","year":"2022","journal-title":"Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s13399-021-01556-0","article-title":"An Eco-Friendly and Sustainable System for Monitoring the Oleuropein-Rich Extract from Olive Tree (Olea europaea) Leaves","volume":"12","year":"2022","journal-title":"Biomass Convers. Biorefin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1016\/j.jksus.2020.01.017","article-title":"Plant-Mediated Biosynthesis of Zein\u2013Pectin Nanoparticle: Preparation, Characterization and In Vitro Drug Release Study","volume":"32","author":"Thankappan","year":"2020","journal-title":"J. King Saud Univ. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.foodchem.2017.05.142","article-title":"Encapsulation of Antioxidant Phenolic Compounds Extracted from Spent Coffee Grounds by Freeze-Drying and Spray-Drying Using Different Coating Materials","volume":"237","author":"Ballesteros","year":"2017","journal-title":"Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.cep.2006.06.020","article-title":"The Physicochemical Properties of Spray-Dried Watermelon Powders","volume":"46","author":"Quek","year":"2007","journal-title":"Chem. Eng. Process. Process Intensif."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0378-5173(02)00604-X","article-title":"Spray-Dried Chitinosans: Part I: Preparation and Characterization","volume":"252","author":"Rege","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_19","first-page":"197","article-title":"Effect of Spray-Freeze Drying Process on Physical Properties of Maltodextrin","volume":"43","year":"2018","journal-title":"GIDA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/pca.1129","article-title":"A Simple Isocratic HPLC Method for the Simultaneous Determination of Curcuminoids in Commercial Turmeric Extracts","volume":"20","author":"Wichitnithad","year":"2009","journal-title":"Phytochem. Anal."},{"key":"ref_21","first-page":"e17047","article-title":"Encapsulation and In Vitro Evaluation of Phenolic Compounds of Propolis by Spray and Freeze Drying","volume":"46","author":"Baysan","year":"2022","journal-title":"J. Food Process. Preserv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1039\/C3FO60702J","article-title":"A Standardised Static In Vitro Digestion Method Suitable for Food\u2014An International Consensus","volume":"5","author":"Minekus","year":"2014","journal-title":"Food Funct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23623","DOI":"10.1007\/s13399-023-04366-8","article-title":"Green Synthesis and Characterization of Selenium Nanoparticles (Se NPs) from the Skin (Testa) of Pistacia vera L. (Siirt Pistachio) and Investigation of Antimicrobial and Anticancer Potentials","volume":"14","author":"Baran","year":"2023","journal-title":"Biomass Convers. Biorefin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.4103\/jcrt.jcrt_1886_21","article-title":"Antiproliferative Effect of Potentilla fulgens on Glioblastoma Cancer Cells through Downregulation of Akt\/MTOR Signaling Pathway","volume":"19","author":"Kandemir","year":"2023","journal-title":"J. Cancer Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11060","DOI":"10.1021\/cr300162p","article-title":"Deep Eutectic Solvents (DESs) and Their Applications","volume":"114","author":"Smith","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"460730","DOI":"10.1016\/j.chroma.2019.460730","article-title":"In Situ Formation of Thymol-Based Hydrophobic Deep Eutectic Solvents: Application to Antibiotics Analysis in Surface Water Based on Liquid-Liquid Microextraction Followed by Liquid Chromatography","volume":"1614","author":"Li","year":"2020","journal-title":"J. Chromatogr. A"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1021\/acs.jnatprod.7b00945","article-title":"Natural Deep Eutectic Solvents: Properties, Applications, and Perspectives","volume":"81","author":"Liu","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bagovi\u0107 Koli\u0107, M., \u017deleznjak, M., Markov, K., Gaurina Sr\u010dek, V., Cvjetko Bubalo, M., Rado\u0161evi\u0107, K., and Radoj\u010di\u0107 Redovnikovi\u0107, I. (2025). Physicochemical and Biological Properties of Menthol and Thymol-Based Natural Deep Eutectic Solvents. Molecules, 30.","DOI":"10.3390\/molecules30081713"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.cis.2003.10.023","article-title":"Formation and Stability of Nano-Emulsions","volume":"108\u2013109","author":"Tadros","year":"2004","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.5530\/srp.2017.1.8","article-title":"Emulsion Micro Emulsion and Nano Emulsion: A Review","volume":"8","author":"Kale","year":"2017","journal-title":"Syst. Rev. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Danaei, M., Dehghankhold, M., Ataei, S., Hasanzadeh Davarani, F., Javanmard, R., Dokhani, A., Khorasani, S., and Mozafari, M.R. (2018). Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020057"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1365-2621.1977.tb12569.x","article-title":"The Role of the Specimen Dimensions in Uniaxial Compression of Food Materials","volume":"42","author":"Peleg","year":"1977","journal-title":"J. Food Sci."},{"key":"ref_33","first-page":"163","article-title":"Evaluating Flow Properties of Solids","volume":"18","author":"Carr","year":"1965","journal-title":"Chem. Eng. J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mohammed, N.K., Tan, C.P., Manap, Y.A., Muhialdin, B.J., and Hussin, A.S.M. (2020). Spray Drying for the Encapsulation of Oils\u2014A Review. Molecules, 25.","DOI":"10.3390\/molecules25173873"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"\u010culina, P., Zori\u0107, Z., Garofuli\u0107, I.E., Repaji\u0107, M., Dragovi\u0107-Uzelac, V., and Pedisi\u0107, S. (2023). Optimization of the Spray-Drying Encapsulation of Sea Buckthorn Berry Oil. Foods, 12.","DOI":"10.3390\/foods12132448"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"125328","DOI":"10.1016\/j.foodchem.2019.125328","article-title":"Enhancing the Oral Bioavailability of Curcumin Using Solid Lipid Nanoparticles","volume":"302","author":"Ban","year":"2020","journal-title":"Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Boccellino, M., Ambrosio, P., Ballini, A., De Vito, D., Scacco, S., Cantore, S., Feola, A., Di Donato, M., Quagliuolo, L., and Sciarra, A. (2022). The Role of Curcumin in Prostate Cancer Cells and Derived Spheroids. Cancers, 14.","DOI":"10.3390\/cancers14143348"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41598-024-82687-y","article-title":"The Anticancer Activity of Fucoidan Coated Selenium Nanoparticles and Curcumin Nanoparticles against Colorectal Cancer Lines","volume":"15","author":"Alduais","year":"2025","journal-title":"Sci. Rep."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/15\/2601\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:04:34Z","timestamp":1785229474000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/15\/2601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":38,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["foods15152601"],"URL":"https:\/\/doi.org\/10.3390\/foods15152601","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}