{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:47:23Z","timestamp":1792806443844,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Istanbul Kent University","award":["BAP 2024\/3"],"award-info":[{"award-number":["BAP 2024\/3"]}],"id":[{"id":"https:\/\/ror.org\/01w9wgg77","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tribor R&D Chemical Industry Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Liposomes and niosomes are established drug delivery systems, some of which have received FDA approval and demonstrated therapeutic efficacy. This study investigates a novel niosome formulation, utilizing two natural food-derived components, as a cost-effective alternative to traditional nanocarriers. The active pharmaceutical ingredient, calcium fructoborate (CF), possesses notable anti-inflammatory properties. The study aims to evaluate the efficacy of this novel natural niosome (NN) system, in comparison to existing nanocarrier formulations, in an ischemia\u2013reperfusion (I\/R) pain model. Methods: An acute ischemia\/reperfusion injury model was employed to induce pain in 36 rats. The efficacy of the following treatments was assessed: standard CF, liposomal CF, niosomal CF, and natural niosomal CF. Efficacy was determined by quantifying the treatments\u2019 ability to mitigate inflammation and oxidative stress in the kidneys, lungs, heart, and liver, and by evaluating potential organ damage through histopathological analysis. Results: The NN treatment significantly reduced malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-\u03b1) levels in the kidneys and liver compared to the other treatments (p &lt; 0.05). In the kidney, NN treatment also significantly decreased creatinine levels relative to the other treatments (p &lt; 0.01). The histopathological analysis of kidney tissue revealed that NN treatment attenuated tubular dilation, interstitial inflammation, and epithelial thinning. In the heart, liposomal treatment significantly increased MDA levels (p &lt; 0.05) and decreased sialic acid levels (p &lt; 0.05); however, no significant differences were observed in troponin levels (p &gt; 0.05). In the lung, no significant differences in MDA, lactate, TNF-\u03b1, or sialic acid levels were detected among the treatment groups (p &gt; 0.05). Conclusions: The natural niosome drug delivery system demonstrates potential as a therapeutic intervention for protecting and improving kidney and liver health. While liposomal treatment exhibited some adverse effects, it effectively suppressed inflammation. This study provides a foundation for future research and positions the NN drug delivery system as a promising, cost-effective alternative for inflammation-associated pathologies.<\/jats:p>","DOI":"10.3390\/pharmaceutics17111434","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:02:03Z","timestamp":1762419723000},"page":"1434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficiency of Calcium Fructoborate-Loaded Novel Natural Niosomes Compared to Traditional Liposomes and Niosomes in Rat Ischemia\u2013Reperfusion Injury Model"],"prefix":"10.3390","volume":"17","author":[{"given":"Kubra","family":"Vardar","sequence":"first","affiliation":[{"name":"Department of Pharmacy Services, Vocational School of Health Services, Istanbul Kent University, 34406 Istanbul, T\u00fcrkiye"},{"name":"Tribor R&D Chemical Industry Ltd., Yildiz Technical University Technopark, 34490 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-379X","authenticated-orcid":false,"given":"Nilufer","family":"Kara","sequence":"additional","affiliation":[{"name":"Tribor R&D Chemical Industry Ltd., Yildiz Technical University Technopark, 34490 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6691-3494","authenticated-orcid":false,"given":"Nuri Murat","family":"Ozayman","sequence":"additional","affiliation":[{"name":"Tribor R&D Chemical Industry Ltd., Yildiz Technical University Technopark, 34490 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-9917","authenticated-orcid":false,"given":"Kubilay","family":"Gocucu","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques, Vocational School of Health Services, Istanbul Kent University, 34406 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirin Funda","family":"Eren","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques, Vocational School of Health Services, Istanbul Kent University, 34406 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metin","family":"Plevneli","sequence":"additional","affiliation":[{"name":"Independent Researcher, 34100 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Aslan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Hamidiye Faculty of Pharmacy, University of Health Sciences, 34668 Istanbul, T\u00fcrkiye"},{"name":"Faculty of Pharmacy, Istanbul Kent University, 34406 Istanbul, T\u00fcrkiye"},{"name":"SFA R&D & Private Health Services Co., Ltd., Teknopark Blv. No1 3A Z01, Teknopark \u0130stanbul, 34906 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Necmettin","family":"Atsu","sequence":"additional","affiliation":[{"name":"Department of Nursing, Faculty of Health Sciences, Istanbul Kent University, 34406 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pandita, D., Poonia, N., Chaudhary, G., Jain, G.K., Lather, V., and Khar, R.K. (2022). pH-sensitive polymeric nanocarriers for enhanced intracellular drug delivery. Smart Polymeric Nano-Constructs in Drug Delivery: Concept, Design and Therapeutic Applications, Elsevier.","DOI":"10.1016\/B978-0-323-91248-8.00004-0"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Urb\u00e1n-Morl\u00e1n, Z., Serrano-Mora, L.E., Mart\u00ednez-Acevedo, L., Leyva-G\u00f3mez, G., Mendoza-Mu\u00f1oz, N., and Quintanar-Guerrero, D. (2020). New developments in intrauterine drug delivery systems and devices. Drug Delivery Devices and Therapeutic Systems, Elsevier.","DOI":"10.1016\/B978-0-12-819838-4.00018-3"},{"key":"ref_3","first-page":"801820","article-title":"Lipid-Based Drug Delivery Systems","volume":"2014","author":"Shrestha","year":"2014","journal-title":"J. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jconrel.2021.05.032","article-title":"Solid lipid nanoparticles for hydrophilic drugs","volume":"335","author":"Mirchandani","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0009-3084(93)90071-A","article-title":"Liposomes: The Babraham connection","volume":"64","author":"Bangham","year":"1993","journal-title":"Chem. Phys. Lipids"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3109\/21691401.2014.953633","article-title":"Application of liposomes in medicine and drug delivery","volume":"44","author":"Daraee","year":"2016","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0031-6997(25)06651-7","article-title":"Biological approaches to the controlled delivery of drugs: A critical review","volume":"36","author":"Poznansky","year":"1984","journal-title":"Pharmacol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Liga, S., Paul, C., Moac\u0103, E.-A., and P\u00e9ter, F. (2024). Niosomes: Composition, Formulation Techniques, and Recent Progress as Delivery Systems in Cancer Therapy. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16020223"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3109\/10717544.2013.838077","article-title":"Recent Advances in Non-Ionic Surfactant Vesicles (Niosomes): Self-Assembly, Fabrication, Characterization, Drug Delivery Applications and Limitations","volume":"21","author":"Abdelkader","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1055\/s-0042-110495","article-title":"Saponins from Saponaria officinalis L. Augment the Efficacy of a Rituximab-Immunotoxin","volume":"82","author":"Thakur","year":"2016","journal-title":"Planta Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jcis.2020.04.061","article-title":"Surfactant\/biosurfactant mixing: Adsorption of saponin\/nonionic surfactant mixtures at the air-water interface","volume":"574","author":"Tucker","year":"2020","journal-title":"J. Colloid Interface Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.jff.2015.03.009","article-title":"Squalene targets pro- and anti-inflammatory mediators and pathways to modulate over-activation of neutrophils, monocytes and macrophages","volume":"14","author":"Bermudez","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ibrahim, N.I., Fairus, S., Zulfarina, M.S., and Naina Mohamed, I. (2020). The Efficacy of Squalene in Cardiovascular Disease Risk\u2014Systematic Review. Nutrients, 12.","DOI":"10.3390\/nu12020414"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/B978-0-12-416003-3.00014-7","article-title":"Biological Importance and Applications of Squalene and Squalane","volume":"Volume 65","author":"Kim","year":"2012","journal-title":"Advances in Food and Nutrition Research"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6238","DOI":"10.1073\/pnas.83.17.6238","article-title":"The pseudopterosins: Anti-Inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae","volume":"83","author":"Look","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0166-3542(99)00036-4","article-title":"Antiviral properties of isoborneol, a potent inhibitor of herpes simplex virus type 1","volume":"43","author":"Armaka","year":"1999","journal-title":"Antivir. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s12011-011-8972-6","article-title":"Calcium fructoborate\u2014Potential anti-inflammatory agent","volume":"143","author":"Scorei","year":"2011","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12011-007-0019-7","article-title":"In vitro effects of calcium fructoborate on fMLP-stimulated human neutrophil granulocytes","volume":"118","author":"Scorei","year":"2007","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/jbmr.5650090206","article-title":"Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick","volume":"9","author":"Hunt","year":"1994","journal-title":"J. Bone Miner. Res."},{"key":"ref_20","unstructured":"(2025, January 19). Arsenic, Boron, Nickel, Silicon, and Vanadium, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK222322\/."},{"key":"ref_21","unstructured":"National Institutes of Health, Office of Dietary Supplements (2025, January 19). Boron\u2014Health Professional Fact Sheet, Available online: https:\/\/ods.od.nih.gov\/factsheets\/Boron-HealthProfessional."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1159\/000520430","article-title":"Fluid Resuscitation Aggravates the Cellular Injury in a Hemorrhagic Shock Model","volume":"5","author":"Vardar","year":"2022","journal-title":"Dubai Med. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2478\/jtim-2022-0045","article-title":"Hypervolemia Suppresses dilutional anaemic injury in a rat model of haemodilution","volume":"11","author":"Cakir","year":"2023","journal-title":"J. Transl. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jss.2019.03.012","article-title":"An empirical study on pareto based multi-objective feature selection for software defect prediction","volume":"152","author":"Ni","year":"2019","journal-title":"J. Syst. Softw."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0076-6879(78)52032-6","article-title":"Microsomal lipid peroxidation","volume":"52","author":"Buege","year":"1978","journal-title":"Methods Enzymol."},{"key":"ref_27","first-page":"1721","article-title":"A simplified quick method for determination of sialic acid in serum","volume":"44","author":"Sydow","year":"1985","journal-title":"Biomed. Biochim. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.tca.2010.04.006","article-title":"Thermal analysis of a calcium fructoborate sample","volume":"506","author":"Rotaru","year":"2010","journal-title":"Thermochim. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"F1026","DOI":"10.1152\/ajprenal.00281.2013","article-title":"Renal oxygenation in acute renal ischemia-reperfusion injury","volume":"306","author":"Abdelkader","year":"2014","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nature05292","article-title":"Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases","volume":"443","author":"Lin","year":"2006","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1385\/BTER:107:2:127","article-title":"In vitro evaluation of the antioxidant activity of calcium fructoborate","volume":"107","author":"Scorei","year":"2005","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Inglut, C.T., Sorrin, A.J., Kuruppu, T., Vig, S., Cicalo, J., Ahmad, H., and Huang, H.-C. (2020). Immunological and Toxicological Considerations for the Design of Liposomes. Nanomaterials, 10.","DOI":"10.3390\/nano10020190"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41573-021-00233-1","article-title":"Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy","volume":"20","author":"Forman","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Moammeri, A., Chegeni, M.M., Sahrayi, H., Ghafelehbashi, R., Memarzadeh, F., Mansouri, A., Akbarzadeh, I., Abtahi, M.S., Hejabi, F., and Ren, Q. (2023). Current advances in niosomes applications for drug delivery and cancer treatment. Mater. Today Bio, 23.","DOI":"10.1016\/j.mtbio.2023.100837"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s00467-015-3169-4","article-title":"Tubular atrophy in the pathogenesis of chronic kidney disease progression","volume":"31","author":"Schelling","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Godoy, J.R., Watson, G., Raspante, C., and Illanes, O. (2021). An Effective Mouse Model of Unilateral Renal Ischemia-Reperfusion Injury. JoVE, 62749.","DOI":"10.3791\/62749"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/11\/1434\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:08:53Z","timestamp":1762420133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/11\/1434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["pharmaceutics17111434"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17111434","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]}}}