{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:54:42Z","timestamp":1774896882954,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European funding program POC-A1-A1.2.3-G-2015, ID P_40_321, MySMIS code 105509","award":["57\/05.09.2016"],"award-info":[{"award-number":["57\/05.09.2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Achieving and maintaining a well-balanced immune system has righteously become an insightful task for the general population and an even more fundamental goal for those affected by immune-related diseases. Since our immune functions are indispensable in defending the body against pathogens, diseases and other external attacks, while playing a vital role in maintaining health and modulating the immune response, we require an on-point grasp of their shortcoming as a foundation for the development of functional foods and novel nutraceuticals. Seeing that immunoceuticals are considered effective in improving immune functions and reducing the incidence of immunological disorders, the main focus of this study was to assess the immunomodulatory properties and possible acute toxicity of a novel nutraceutical with active substances of natural origin on C57BL\/6 mice for 21 days. We evaluated the potential hazards (microbial contamination and heavy metals) of the novel nutraceutical and addressed the acute toxicity according to OECD guidelines of a 2000 mg\/kg dose on mice for 21 days. The immunomodulatory effect was assessed at three concentrations (50 mg\/kg, 100 mg\/kg and 200 mg\/kg) by determining body and organ indexes through a leukocyte analysis; flow cytometry immunophenotyping of lymphocytes populations and their subpopulations (T lymphocytes (LyCD3+), cytotoxic suppressor T lymphocytes (CD3+CD8+), helper T lymphocytes (CD3+CD4+), B lymphocytes (CD3\u2212CD19+) and NK cells (CD3\u2212NK1.1.+); and the expression of the CD69 activation marker. The results obtained for the novel nutraceutical referred to as ImunoBoost indicated no acute toxicity, an increased number of lymphocytes and the stimulation of lymphocyte activation and proliferation, demonstrating its immunomodulatory effect. The safe human consumption dose was established at 30 mg\/day.<\/jats:p>","DOI":"10.3390\/pharmaceutics15041292","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T04:53:59Z","timestamp":1681966439000},"page":"1292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["In Vivo Acute Toxicity and Immunomodulation Assessment of a Novel Nutraceutical in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Tatiana","family":"Onisei","sequence":"first","affiliation":[{"name":"The National Institute for Research and Development in Food Bioresources, Dinu Vintil\u0103 Street, No.6, 021102 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca-Maria","family":"Tih\u0103uan","sequence":"additional","affiliation":[{"name":"The National Institute for Research and Development in Food Bioresources, Dinu Vintil\u0103 Street, No.6, 021102 Bucharest, Romania"},{"name":"Research Institute of the University of Bucharest\u2014ICUB, 91\u201395 Spl. Independentei, 50567 Bucharest, Romania"},{"name":"Research & Development for Advanced Biotechnologies and Medical Devices, SC Sanimed International Impex SRL, 087040 C\u0103lug\u0103reni, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9924-1987","authenticated-orcid":false,"given":"Georgiana","family":"Dolete","sequence":"additional","affiliation":[{"name":"Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 011061 Bucharest, Romania"},{"name":"National Research Center for Food Safety, University Politehnica of Bucharest, 060042 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3546-1136","authenticated-orcid":false,"given":"M\u0103d\u0103lina","family":"Axinie (Bucos)","sequence":"additional","affiliation":[{"name":"Research & Development for Advanced Biotechnologies and Medical Devices, SC Sanimed International Impex SRL, 087040 C\u0103lug\u0103reni, Romania"},{"name":"Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 011061 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"R\u0103scol","sequence":"additional","affiliation":[{"name":"The National Institute for Research and Development in Food Bioresources, Dinu Vintil\u0103 Street, No.6, 021102 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gheorghi\u021ba","family":"Isvoranu","sequence":"additional","affiliation":[{"name":"National Institute of Pathology Victor Babe\u015f\u2014Bucharest, 99-101 Spl. 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Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/1471-0307.12421","article-title":"Immunomodulation by hydrolysates and peptides derived from milk proteins","volume":"71","year":"2018","journal-title":"Int. J. Dairy Technol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00216-009-2838-1","article-title":"Immunomodulation by food: Promising concept for mitigating allergic disease?","volume":"395","author":"Wichers","year":"2009","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.3389\/fnut.2022.1082500","article-title":"The relationship between nutrition and the immune system","volume":"9","author":"Munteanu","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Weyh, C., Kr\u00fcger, K., Peeling, P., and Castell, L. (2022). The Role of Minerals in the Optimal Functioning of the Immune System. Nutrients, 14.","DOI":"10.3390\/nu14030644"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gombart, A.F., Pierre, A., and Maggini, S. (2020). A Review of Micronutrients and the Immune System\u2013Working in Harmony to Reduce the Risk of Infection. Nutrients, 12.","DOI":"10.3390\/nu12010236"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1038\/s41430-021-00960-z","article-title":"Cellular and metabolic mechanisms of nutrient actions in immune function","volume":"75","author":"Newsholme","year":"2021","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s40279-019-01160-3","article-title":"Nutrition and Athlete Immune Health: New Perspectives on an Old Paradigm","volume":"49","author":"Walsh","year":"2019","journal-title":"Sport. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4110\/in.2017.17.1.13","article-title":"The Specific Roles of Vitamins in the Regulation of Immunosurveillance and Maintenance of Immunologic Homeostasis in the Gut","volume":"17","author":"Hosomi","year":"2017","journal-title":"Immune Netw."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.3389\/fimmu.2021.637553","article-title":"Medicinal Plants and Isolated Molecules Demonstrating Immunomodulation Activity as Potential Alternative Therapies for Viral Diseases Including COVID-19","volume":"12","author":"Alhazmi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/B978-0-12-394591-4.00004-0","article-title":"Developing Phytocompounds from Medicinal Plants as Immunomodulators","volume":"62","author":"Wen","year":"2012","journal-title":"Adv. Bot. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Aye, M.M., Aung, H.T., Sein, M.M., and Armijos, C. (2019). A Review on the Phytochemistry, Medicinal Properties and Pharmacological Activities of 15 Selected Myanmar Medicinal Plants. Molecules, 24.","DOI":"10.3390\/molecules24020293"},{"key":"ref_15","first-page":"2343","article-title":"Bilberries: Curative and Miraculous\u2014A Review on Bioactive Constituents and Clinical Research","volume":"13","author":"Rollinger","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4103\/0973-7847.156353","article-title":"Echinacea purpurea: Pharmacology, phytochemistry and analysis methods","volume":"9","author":"Saeidnia","year":"2015","journal-title":"Pharmacogn. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"\u0218tef\u0103nescu, R., Laczk\u00f3-Z\u00f6ld, E., \u0150sz, B.-E., and Vari, C.-E. (2023). An Updated Systematic Review of Vaccinium myrtillus Leaves: Phytochemistry and Pharmacology. Pharmaceutics, 15.","DOI":"10.37766\/inplasy2022.12.0029"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tieu, S., Charchoglyan, A., Wagter-Lesperance, L., Karimi, K., Bridle, B.W., Karrow, N.A., and Mallard, B.A. (2022). Immunoceuticals: Harnessing Their Immunomodulatory Potential to Promote Health and Wellness. Nutrients, 14.","DOI":"10.3390\/nu14194075"},{"key":"ref_19","unstructured":"(2005). European Pharmacopoeia, 5th Edition, Main Volume 5.0 with Supplements 5.1 and 5.2, Council of Europe."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Birhanu, B.T., Kim, J.-Y., Hossain, A., Choi, J.-W., Lee, S.-P., and Park, S.-C. (2018). An in vivo immunomodulatory and anti-inflammatory study of fermented Dendropanax morbifera L\u00e9veille leaf extract. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2282-x"},{"key":"#cr-split#-ref_21.1","unstructured":"European Commission (2006). Commission Regulation"},{"key":"#cr-split#-ref_21.2","unstructured":"(EC) No 1881\/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs (Text with EEA relevance). Off. J. Eur. Union., 364, 5-24."},{"key":"ref_22","first-page":"12","article-title":"Beneficial effects of food supplements based on hydrolyzed collagen for skin care (Review)","volume":"20","author":"Lupu","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Soutelino, M.E.M., Rocha, R.D., de Oliveira, B.C.R., M\u00e1rsico, E.T., and de Silva, A.C.O. (2022). Technological aspects and health effects of hydrolyzed collagen and application in dairy products. Crit. Rev. Food Sci. Nutr., 1\u20139.","DOI":"10.1080\/10408398.2022.2163974"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.1016\/j.joca.2014.02.240","article-title":"Hydrolyzed collagen contributes to osteoblast differentiation in vitro and subsequent bone health in vivo","volume":"22","author":"Daneault","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1097\/MCO.0000000000000870","article-title":"Collagen peptide supplementation for pain and function: Is it effective?","volume":"25","author":"Kviatkovsky","year":"2022","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_26","first-page":"2011","article-title":"Exploration of collagen recovered from animal by-products as a precursor of bioactive peptides: Successes and challenges","volume":"59","author":"Fu","year":"2018","journal-title":"Food Sci. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Le\u00f3n-L\u00f3pez, A., P\u00e9rez-Marroqu\u00edn, X.A., Campos-Lozada, G., Campos-Montiel, R.G., and Aguirre-\u00c1lvarez, G. (2020). Characterization of Whey-Based Fermented Beverages Supplemented with Hydrolyzed Collagen: Antioxidant Activity and Bioavailability. Foods, 9.","DOI":"10.3390\/foods9081106"},{"key":"ref_28","first-page":"129","article-title":"Health Benefits of Whey Protein: A Review","volume":"2","author":"Solak","year":"2012","journal-title":"J. Food Sci. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.3168\/jds.2020-19038","article-title":"Invited review: Acid whey trends and health benefits","volume":"104","author":"Kosmerl","year":"2021","journal-title":"J. Dairy Sci."},{"key":"ref_30","first-page":"495","article-title":"Whey Based Beverage: Its Functionality, Formulations, Health Benefits and Applications","volume":"6","author":"Chavan","year":"2015","journal-title":"J. Food Process. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Blair, M., Kellow, N.J., Dordevic, A.L., Evans, S., Caissutti, J., and McCaffrey, T.A. (2020). Health Benefits of Whey or Colostrum Supplementation in Adults \u226535 Years; a Systematic Review. Nutrients, 12.","DOI":"10.3390\/nu12020299"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ahmad, S., Campos, M.G., Fratini, F., Altaye, S.Z., and Li, J. (2020). New Insights into the Biological and Pharmaceutical Properties of Royal Jelly. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020382"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Viuda-Martos, M., P\u00e9rez-Alvarez, J.A., and Fern\u00e1ndez-L\u00f3pez, J. (2017). Royal jelly: Health benefits and uses in medicine. Bee Prod. Chem. Biol. Prop., 199\u2013218.","DOI":"10.1007\/978-3-319-59689-1_10"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Collazo, N., Carpena, M., Nu\u00f1ez-Estevez, B., Otero, P., Simal-Gandara, J., and Prieto, M.A. (2021). Health Promoting Properties of Bee Royal Jelly: Food of the Queens. Nutrients, 13.","DOI":"10.3390\/nu13020543"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104514","DOI":"10.1016\/j.jff.2021.104514","article-title":"Active components and biological functions of royal jelly","volume":"82","author":"Guo","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6896","DOI":"10.1021\/jf0511300","article-title":"Antioxidant properties of prepared blueberry (Vaccinium myrtillus) extracts","volume":"53","author":"Faria","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1080\/09540105.2021.1986471","article-title":"Anthocyanins profiling of bilberry (Vaccinium myrtillus L.) extract that elucidates antioxidant and anti-inflammatory effects","volume":"32","author":"Bayazid","year":"2021","journal-title":"Food Agric. Immunol."},{"key":"ref_38","first-page":"3","article-title":"Antioxidants in Herbs and Spices","volume":"9","author":"Paur","year":"2011","journal-title":"Nutr. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.3390\/cimb44100313","article-title":"Anti-Inflammatory Activity of Bilberry (Vaccinium myrtillus L.)","volume":"44","author":"Sharma","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/S1004-9541(08)60234-7","article-title":"Antioxidant and Antimicrobial Activities of Echinacea (Echinacea purpurea L.) Extracts Obtained by Classical and Ultrasound Extraction","volume":"17","author":"Lazic","year":"2009","journal-title":"Chin. J. Chem. Eng."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.foodchem.2005.11.048","article-title":"Antioxidant activity of cichoric acid and alkamides from Echinacea purpurea, alone and in combination","volume":"101","author":"Thygesen","year":"2007","journal-title":"Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Banica, F., Bungau, S., Tit, D.M., Behl, T., Otrisal, P., Nechifor, A.C., Gitea, D., Pavel, F.-M., and Nemeth, S. (2020). Determination of the Total Polyphenols Content and Antioxidant Activity of Echinacea purpurea Extracts Using Newly Manufactured Glassy Carbon Electrodes Modified with Carbon Nanotubes. Processes, 8.","DOI":"10.3390\/pr8070833"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1089\/jmf.2016.3790","article-title":"Antioxidant, Antidiabetic, and Antihypertensive Properties of Echinacea purpurea Flower Extract and Caffeic Acid Derivatives Using In Vitro Models","volume":"20","author":"Chiou","year":"2017","journal-title":"J. Med. Food"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Komala, M.G., Ong, S.G., Qadri, M.U., Elshafie, L.M., Pollock, C.A., and Saad, S. (2023). Investigating the Regulatory Process, Safety, Efficacy and Product Transparency for Nutraceuticals in the USA, Europe and Australia. Foods, 12.","DOI":"10.3390\/foods12020427"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gil, F., Hern\u00e1ndez, A.F., and Mart\u00edn-Domingo, M.C. (2016). Chapter 58. Toxic Contamination of Nutraceuticals and Food Ingredients. Nutraceuticals, 823\u2013838.","DOI":"10.1016\/B978-0-12-802147-7.00058-9"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Orhan, I.E., Senol, F.S., Skalicka-Wozniak, K., Georgiev, M., and Sener, B. (2016). Adulteration and safety issues in nutraceuticals and dietary supplements: Innocent or risky?. Nutraceuticals, 153\u2013182.","DOI":"10.1016\/B978-0-12-804305-9.00005-1"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1080\/01926230490465874","article-title":"Relationships Between Organ Weight and Body\/Brain Weight in the Rat: WhaT Is the Best Analytical Endpoint?","volume":"32","author":"Bailey","year":"2004","journal-title":"Toxicol. Pathol."},{"key":"ref_48","unstructured":"(2022). OECD Guidelines for the Testing of Chemicals, Section 4, OECD."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"111254","DOI":"10.1016\/j.fct.2020.111254","article-title":"A 90 day oral toxicity study of blueberry polyphenols in ovariectomized sprague-dawley rats","volume":"139","author":"Cladis","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_50","first-page":"1076","article-title":"Toxicity of Echinacea purpurea. Acute, subacute and genotoxicity studies","volume":"41","author":"Mengs","year":"1991","journal-title":"Arzneimittelforschung"},{"key":"ref_51","first-page":"186","article-title":"Mucoactive effect evaluation and acute toxicity study of natural herbal combination of echinacea purpurea, sambucus nigra, glycyrrhiza glabra, vitex trifolia, and zingiber officinale","volume":"1","author":"Arifin","year":"2020","journal-title":"Pharmacol. Online"},{"key":"ref_52","first-page":"475","article-title":"Determination of medium lethal dose (ld50 value) for oral acute toxicity of royal jellY Royal jelly on chemotherapeutic drug induced alterations in mice View project neurobehavioral impact of royal jelly in mice View project","volume":"8","author":"Hina","year":"2019","journal-title":"World J. Pharm. Pharm. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1111\/ijfs.13772","article-title":"Hydrolysed collagen from Lates calcarifer skin: Its acute toxicity and impact on cell proliferation and collagen production of fibroblasts","volume":"53","author":"Benjakul","year":"2018","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, H. (2021). A Review of the Effects of Collagen Treatment in Clinical Studies. Polymers, 13.","DOI":"10.3390\/polym13223868"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gurfein, B.T., Hasdemir, B., Milush, J.M., Touma, C., Palme, R., Nixon, D.F., Darcel, N., Hecht, F.M., and Bhargava, A. (2017). Enriched environment and stress exposure influence splenic B lymphocyte composition. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180771"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1172\/JCI111171","article-title":"Functional Heterogeneities among Concanavalin A-activated OKT4\u2019 and OKT8\u2019 Cells by Using Autologous Erythrocyte Rosette Technique","volume":"72","author":"Takada","year":"1983","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Di Sotto, A., Vitalone, A., and Di Giacomo, S. (2020). Plant-Derived Nutraceuticals and Immune System Modulation: An Evidence-Based Overview. Vaccines, 8.","DOI":"10.3390\/vaccines8030468"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"R\u0103ducanu, A.E., Tih\u0103uan, B.-M., Marina\u0219, I.C., Ciuperc\u0103, O.T., \u021aebrencu, C.E., Ionescu, E., and Onisei, T. (2021). The Biological Effects of Novel Nutraceuticals with Curcuminoids and Other Plant-Derived Immunomodulators and Pre-Probiotics. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13050666"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Costagliola, G., Nuzzi, G., Spada, E., Comberiati, P., Verduci, E., and Peroni, D. (2021). Review Nutraceuticals in Viral Infections: An Overview of the Immunomodulating Properties. Nutrients, 13.","DOI":"10.3390\/nu13072410"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1124\/pharmrev.120.000063","article-title":"Pharmacological Modulation of Immune Responses by Nutritional Components","volume":"73","author":"Folkerts","year":"2021","journal-title":"Pharmacol. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/eji.201646837","article-title":"CD69: From activation marker to metabolic gatekeeper","volume":"47","year":"2017","journal-title":"Eur. J. Immunol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/4\/1292\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:19:40Z","timestamp":1760123980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/4\/1292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,20]]},"references-count":62,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["pharmaceutics15041292"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15041292","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,20]]}}}