Evaluation of the efficacy of rutin, rutin nanocrystals, and rutin spanlastics nanoparticles as antitumor and antioxidant drug delivery systems
Source abstract
Abstract
Flavonoids comprise an exclusive class of biomolecules with extensive therapeutic features. Rutin is one of the flavonoids that has antioxidant, anticancer, and other pharmacological actions, but its clinical use is deterred by poor solubility, poor bioavailability, and incomplete absorption. Development of nanotechnology-based delivery platforms is a promising solution to counter these issues. We evaluated the antioxidant and anticancer properties of nanocrystals and spanlastic nanoparticles of rutin against the human breast adenocarcinoma cell line MCF-7 to establish effective delivery methods with improved therapeutic efficacy. The physicochemical characteristics of the nano-formulations were investigated through particle size and zeta potential measurement, Fourier Transform Infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), electronic bandgap energy, and dissolution behavior. Antioxidant activity was investigated through DPPH and ABTS radical scavenger assays. Anticancer potential was established through a viability assay, cell cycle analysis, dual labeling with annexin-V/propidium iodide (PI) (using fluorescence-activated flow cytometric methods), and Caspase 3 activity. Rutin spanlastic nanoparticles showed a considerably smaller particle size, homogeneous dispersion, and negative zeta potential, indicating stability. Rutin spanlastic nanoparticles exhibited greater antioxidant activity compared with free rutin and rutin nanocrystals, as manifested through stronger inhibition of the viability of MCF-7 cells, stronger induction of apoptosis (annexin-V/PI double staining and Caspase 3 activity), and significant G1/0 phase cell cycle arrest. These observations imply an increased solubilization and elastovesicular behaviour of spanlastic nanoparticles with enhanced bioactivity of rutin. In conclusion, rutin spanlastic nanoparticles are an efficient delivery vehicle compared to rutin nanocrystals or free rutin in amplifying both antioxidant and anticancer activity, hence warranting further in vivo experiments to treat breast carcinoma.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Phytochemicals and Antioxidant Activities · Saffron Plant Research Studies · Bioactive Compounds in Plants
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (65)
Show source-provided references
1. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12:31–46. https://doi.org/10.1158/2159-8290.CD-21-1059.10.1158/2159-8290.CD-21-1059 ↗
2. Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, et al. Breast cancer development and progression: risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis. 2018;5:77–106. https://doi.org/10.1016/j.gendis.2018.05.001.10.1016/j.gendis.2018.05.001 ↗
3. Xu X, Li M, Hu J, Chen Z, Yu J, Dong Y, et al. Somatic mitochondrial DNA D-loop mutations in meningioma discovered: a preliminary data a comprehensive overview of mitochondrial DNA 4977-bp. J Cancer Res Ther. 2018;14:1525–34. https://doi.org/10.4103/jcrt.JCRT.10.4103/jcrt.JCRT ↗
4. Ullah A, Munir S, Badshah SL, Khan N, Ghani L, Poulson BG, et al. Important flavonoids and their role as therapeutic agent. Molecules. 2020;25:1–39. https://doi.org/10.3390/molecules25225243.10.3390/molecules25225243 ↗
5. Caglayan C, Kandemir FM, Yildirim S, Kucukler S, Eser G. Rutin protects mercuric chloride-induced nephrotoxicity via targeting of aquaporin 1 levels, oxidative stress, apoptosis, and inflammation in rats. J Trace Elem Med Biol. 2019;54:69–78. https://doi.org/10.1016/j.jtemb.2019.04.007.10.1016/j.jtemb.2019.04.007 ↗
6. Çelik H, Kandemir FM, Caglayan C, Özdemir S, Çomaklı S, Kucukler S, et al. Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation, and apoptosis in rat brain associated with the CREB/BDNF expressions. Mol Biol Rep. 2020;47:2023–34. https://doi.org/10.1007/s11033-020-05302-z.10.1007/s11033-020-05302-z ↗
7. Qanash H, Al-Rajhi AMH, Almashjary MN, Basabrain AA, Hazzazi MS, Abdelghany TM. Inhibitory potential of rutin and rutin nano-crystals against Helicobacter pylori, colon cancer, hemolysis, and butyrylcholinesterase in vitro and in silico. Appl Biol Chem. 2023. https://doi.org/10.1186/s13765-023-00832-z.10.1186/s13765-023-00832-z ↗
8. Chang C, Jia R, Fang B, Miao Y, Zhang L. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer. Open Med. 2025. https://doi.org/10.1515/med-2024-1079.10.1515/med-2024-1079 ↗
9. Akaras N, Kandemir FM, Simşek H, Gür C, Aygörmez S. Antioxidant, antiinflammatory, and antiapoptotic effects of rutin in spleen toxicity induced by sodium valproate in rats. Turk Doga Fen Derg. 2023;12:138–44. https://doi.org/10.46810/tdfd.1299663.10.46810/tdfd.1299663 ↗
10. Imani A, Maleki N, Bohlouli S, Kouhsoltani M, Sharifi S, Maleki Dizaj S. Molecular mechanisms of anticancer effect of rutin. Phytother Res. 2021;35:2500–13. https://doi.org/10.1002/ptr.6977.10.1002/ptr.6977 ↗
11. Malekpour M, Ebrahiminezhad A, Karimi Z, Saadi MI, Berenjian A. Current strategies for rutin nano-formulation; a promising bioactive compound with increased efficacy. Bioprocess Biosyst Eng. 2025;48:877–98. https://doi.org/10.1007/s00449-025-03156-y.10.1007/s00449-025-03156-y ↗
12. Hassan AS, Soliman GM. Rutin nanocrystals with enhanced anti-inflammatory activity: preparation and ex vivo/in vivo evaluation in an inflammatory rat model. Pharmaceutics. 2022;14(12):2727. https://doi.org/10.3390/pharmaceutics14122727.10.3390/pharmaceutics14122727 ↗
13. Rajendran S, Ravi SN, Nair VMR, Sree P, Packirisamy ASB, Palanivelu J. Recent development and future aspects: nano-based drug delivery system in cancer therapy. Top Catal. 2024;67:203–17. https://doi.org/10.1007/s11244-023-01893-6.10.1007/s11244-023-01893-6 ↗
14. Sun L, Liu H, Ye Y, Islam R, Tan T, Tong R, et al. Smart nanoparticles for cancer therapy. Sig Transduct Target Ther. 2023;8:418. https://doi.org/10.1038/s41392-023-01642-x.10.1038/s41392-023-01642-x ↗
15. Losada-Barreiro S, Celik S, Sezgin-Bayindir Z, Bravo-Fernández S, Bravo-Díaz C. Carrier systems for advanced drug delivery: improving drug solubility/bioavailability and administration routes. Pharmaceutics. 2024;16(7):852. https://doi.org/10.3390/pharmaceutics16070852.10.3390/pharmaceutics16070852 ↗
16. Sandri G, Bonferoni MC, Ferrari F, Rossi S, Caramella CM. The Role of Particle Size in Drug Release and Absorption. In: Merkus, H., Meesters, G. (eds.) Particulate Products. 2014; Particle Technology Series, 19. Springer, Cham. https://doi.org/10.1007/978-3-319-00714-41110.1007/978-3-319-00714-411 ↗
17. Singh H, Balusamy SR, Sukweenadhi J, Saravanan M, Aruchamy M, Mijakovic I, et al. Smart hybrid nanomaterials for chronic infections: microbiome-responsive and sustainable therapeutic platforms. J Nanobiotechnol. 2025;23:698. https://doi.org/10.1186/s12951-025-03712-4.10.1186/s12951-025-03712-4 ↗
18. Padarthi PK, Kalvimoorthi V, Challa RR, Vallamkonda B, Grandhe N, Dogiparthi LK, et al. Non-ionic surfactant vesicles (niosomes): structure, functions, classification, and its advances in enhanced drug delivery. Recent Adv Drug Deliv Formul. 2025;19(2):87–104. https://doi.org/10.2174/0126673878322982241126103404.10.2174/0126673878322982241126103404 ↗
19. Pirojiya H, Dudhat K. Niosomes: a revolution in sustainable and targeted drug delivery-green synthesis, precision medicine, and beyond. Regen Eng Trans Med. 2025;11:379–415. https://doi.org/10.1007/s40883-024-00373-x.10.1007/s40883-024-00373-x ↗
20. Karati D, Mukherjee S, Prajapati BG. Unveiling spanlastics as a novel carrier for drug delivery: a review. Pharm Nanotechnol. 2025;13(1):133–42. https://doi.org/10.2174/0122117385286921240103113543.10.2174/0122117385286921240103113543 ↗
21. Khan A, Varshney C, Chaudhary T, Singh B. Spanlastics: an innovative formulation strategy in pharmaceutical drug delivery. World J Pharm Res. 2023;12(20):219–34. https://doi.org/10.20959/wjpr202320-30212.10.20959/wjpr202320-30212 ↗
22. Eker F, Duman H, Akdaşçi E, Bolat E, Sarıtaş S, Karav S, et al. A comprehensive review of nanoparticles: from classification to application and toxicity. Molecules. 2024;29(15):3482. https://doi.org/10.3390/molecules29153482.10.3390/molecules29153482 ↗
23. Khan S, Sharma A, Jain V. An overview of nanostructured lipid carriers and its application in drug delivery through different routes. Adv Pharm Bull. 2023;13(3):446–60. https://doi.org/10.34172/apb.2023.056.10.34172/apb.2023.056 ↗
24. Sanchez Rodriguez JJ, Palchoudhury S, Huang J, Speed D, Tiukalova E, Mante G, et al. Intermediate bandgap (IB) Cu3VSxSe4-x nanocrystals as a new class of light absorbing semiconductors. Nanomaterials (Basel). 2026;16(2):82. https://doi.org/10.3390/nano16020082.10.3390/nano16020082 ↗
25. Chauhan C, Sunidhi SK, Kumar R, Sharma T. Band gap tuning and electrical enhancement in PVDF composites via impregnation of binuclear copper (II) complexes Morphological, optical, and electrochemical insights. Opt Mater. 2025;168:117462. https://doi.org/10.1016/j.optmat.2025.117462.10.1016/j.optmat.2025.117462 ↗
26. Gao Y, Glennon B, He Y, Donnellan P. Dissolution kinetics of a BCS Class II active pharmaceutical ingredient: Diffusion-based model validation and prediction. ACS Omega. 2021;6(12):8056–67. https://doi.org/10.1021/acsomega.0c05558.10.1021/acsomega.0c05558 ↗
27. Fahmy AM, El-Setouhy DA, Ibrahim AB, Habib BA, Tayel SA, Bayoumi NA. Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: in vitro characterization, ex vivo permeation and in vivo biodistribution studies. Drug Deliv. 2018;25(1):12–22. https://doi.org/10.1080/10717544.2017.1410262.10.1080/10717544.2017.1410262 ↗
28. Mazyed EA, Helal DA, Elkhoudary MM, Abd Elhameed AG, Yasser M. Formulation and optimization of nanospanlastics for improving the bioavailability of green tea epigallocatechin gallate. Pharmaceuticals (Basel). 2021;14(1):68. https://doi.org/10.3390/ph14010068.10.3390/ph14010068 ↗
29. Kulkarni SA, Myerson AS. Methods for nano-crystals preparation. In: Roberts K, Docherty R, Tamura R (eds) Engineering crystallography: from molecule to crystal to functional form. NATO Science for Peace and Security Series A: Chemistry and Biology. Springer, Dordrecht. 2017; 275–287. https://doi.org/10.1007/978-94-024-1117-1_1610.1007/978-94-024-1117-1_16 ↗
30. Bhati J, Parvez N, Singh A, Singh P. Development and validation of UV spectrophotometric method for simultaneous estimation of rutin and quercetin in niosome formulation. Der Pharm Lett. 2014;6(3):271–6.
31. Savale S. UV spectrophotometric method development and validation for quantitative estimation of rutin. Hygeia J D Med. 2018;9(2):7–10. https://doi.org/10.15254/H.J.D.Med.9.2018.168.10.15254/H.J.D.Med.9.2018.168 ↗
32. Makuła P, Pacia M, Macyk W. How to correctly determine the band gap energy of modified semiconductor photocatalysts based on UV–vis spectra. J Phys Chem Lett. 2018;9(23):6814.10.1021/acs.jpclett.8b02892 ↗
33. Klein J, Kampermann L, Mockenhaupt B, Behrens M, Strunk J, Bacher G. Limitations of the Tauc plot method. Adv Fun Mat. 2023;33(47):1–19. https://doi.org/10.1002/adfm.202304523.10.1002/adfm.202304523 ↗
34. Abualhasan MN, Mansour J, Jaradat N, Zaid AN, Khadra I. Formulation and development of a validated UV-spectrophotometric analytical method of rutin tablet. Int Sch Res Not. 2017. https://doi.org/10.1155/2017/2624947.10.1155/2017/2624947 ↗
35. Dhote V, Mishra DK, Mishra PK, Dhote K. Micropellets: a promising strategy for controlled release of lansoprazole. Asian J Biomater Res. 2015;1(2):56–61.
36. Kommavarapu P, Maruthapillai A, Palanisamy K. Preparation, characterization, and evaluation of elvitegravir-loaded solid lipid nanoparticles for enhanced solubility and dissolution rate. Trop J Pharm Res. 2015;14(9):1549–56. https://doi.org/10.4314/tjpr.v14i9.2.10.4314/tjpr.v14i9.2 ↗
37. Moraes-de-Souza RA, Oldoni TLC, Regitano-d’Arce MAB, Alencar SM. Antioxidant activity and phenolic composition of herbal infusions consumed in Brazil. Cienc Tecnol Aliment. 2008. https://doi.org/10.1080/11358120809487626.10.1080/11358120809487626 ↗
38. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999. https://doi.org/10.1016/S0891-5849(98)00315-3.10.1016/S0891-5849(98)00315-3 ↗
39. Nie T, Wu H, Wong KH, Chen T. Facile synthesis of highly uniform selenium nanoparticles using glucose as the reductant and surface decorator to induce cancer cell apoptosis. J Mater Chem B. 2016;4(13):2351–8. https://doi.org/10.1039/c5tb02710a.10.1039/c5tb02710a ↗
40. Zhong J, Xia Y, Hua L, Liu X, Xiao M, Xu T, et al. Functionalized selenium nanoparticles enhance the anti-EV71 activity of oseltamivir in human astrocytoma cell model. Artif Cells Nanomed Biotechnol. 2019;47(1):3485–91. https://doi.org/10.1080/21691401.2019.1640716.10.1080/21691401.2019.1640716 ↗
41. Porcu C, Dobrowolny G, Scicchitano BM. Exploring the role of extracellular vesicles in skeletal muscle regeneration. Int J Mol Sci. 2024;25:15811. https://doi.org/10.3390/ijms25115811.10.3390/ijms25115811 ↗
42. Wang N, Hsu C, Zhu L, Tseng S, Hsu JP. Influence of metal oxide nanoparticles concentration on their zeta potential. J Colloid Interface Sci. 2013;407:22–8. https://doi.org/10.1016/j.jcis.2013.05.058.10.1016/j.jcis.2013.05.058 ↗
43. Li C, Chen L, McClements DJ, Peng X, Qiu C, Long J, et al. Preparation and characterization of rutin-loaded carboxymethyl starch nanoparticles. 2022. Foods. https://doi.org/10.3390/foods11182827.10.3390/foods11182827 ↗
44. Khan SA, Khan SB, Khan LU, Farooq A, Akhtar K, Asiri AM. Fourier transform infrared spectroscopy: Fundamentals and application in functional groups and nanomaterials characterization. In: Sharma S, editor. Handbook of materials characterization. Cham: Springer; 2018. https://doi.org/10.1007/978-3-319-92955-2_9.10.1007/978-3-319-92955-2_9 ↗
45. Abdullah BJ. Size effect of band gap in semiconductor nanocrystals and nanostructures from density functional theory within HSE06. Mater Sci Semicond Process. 2022. https://doi.org/10.1016/j.mssp.2021.106214.10.1016/j.mssp.2021.106214 ↗
46. Siepmann J, Siepmann F. Mathematical modeling of drug dissolution. Int J Pharm. 2013;453(1):12–24. https://doi.org/10.1016/j.ijpharm.2013.04.044.10.1016/j.ijpharm.2013.04.044 ↗
47. Kumawat A, Chattopadhyay S, Misra KP, Halder N, Jain SK, Choudhary BL. Blue shift in the optical band gap of sol-gel derived Zn(1-x)SrxO nanoparticles. Solid State Sci. 2020;108:106379. https://doi.org/10.1016/j.solidstatesciences.2020.106379.10.1016/j.solidstatesciences.2020.106379 ↗
48. Malik VK, Pak OS, Feng J. Curvature-assisted vesicle explosion under light-induced asymmetric oxidation. Adv Sci (Weinh). 2024;11(38):e2400504. https://doi.org/10.1002/advs.202400504.10.1002/advs.202400504 ↗
49. Zhu TF, Szostak JW. Exploding vesicles. J Syst Chem. 2011;2:4. https://doi.org/10.1186/1759-2208-2-4.10.1186/1759-2208-2-4 ↗
50. Aleksandrova Y, Neganova M. Antioxidant senotherapy by natural compounds: a beneficial partner in cancer treatment. Antioxidants. 2025. https://doi.org/10.3390/antiox14020199.10.3390/antiox14020199 ↗
51. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8(7):579–91. https://doi.org/10.1038/nrd2803.10.1038/nrd2803 ↗
52. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49(11):1603–16. https://doi.org/10.1016/j.freeradbiomed.2010.09.006.10.1016/j.freeradbiomed.2010.09.006 ↗
53. Uti DE, Atangwho IJ, Alum EU, Ntaobeten E, Obeten UN, Bawa I, et al. Antioxidants in cancer therapy, mitigating lipid peroxidation without compromising treatment through nanotechnology. Discover Nano. 2025. https://doi.org/10.1186/s11671-025-04248-0.10.1186/s11671-025-04248-0 ↗
54. Telang NT. The divergent effects of ovarian steroid hormones in the MCF-7 model for luminal a breast cancer: mechanistic leads for therapy. Int J Mol Sci. 2022;23(9):4800. https://doi.org/10.3390/ijms23094800.10.3390/ijms23094800 ↗
55. Mishra A, Srivastava A, Srivastava A, Sharma LK, Mishra AK, Shrivastava A. Comparative metabolomics of MCF-7 and MCF-7/TAMR identifies potential metabolic pathways in tamoxifen-resistant breast cancer cells. Am J Transl Res. 2024;16(4):1337–52. https://doi.org/10.62347/MJLN5908.10.62347/MJLN5908 ↗
56. Grigalius I, Petrikaite V. Relationship between antioxidant and anticancer activity of trihydroxyflavones. Molecules. 2017. https://doi.org/10.3390/molecules22122169.10.3390/molecules22122169 ↗
57. Lopez-Vidal L, Londoño PS, Rossetti A, Real JP, Paredes AJ, Palma SD. Nanocrystals: Enhancing the Oral Bioavailability of Poorly Soluble Drugs. In: Paredes, A.J. (eds.) Nanocrystals. Springer, Cham. 2026. https://doi.org/10.1007/978-3-032-10238-6_310.1007/978-3-032-10238-6_3 ↗
58. Almohamady HI, Mortagi Y, Gad S, Zaitone S, Alshaman R, Alattar A, et al. Spanlastic nano-vesicles: a novel approach to improve the dissolution, bioavailability, and pharmacokinetic behavior of famotidine. Pharmaceuticals (Basel). 2024;17(12):1614. https://doi.org/10.3390/ph17121614.10.3390/ph17121614 ↗
59. Ou L, Lin S, Song B, Liu J, Lai R, Shao L. The mechanisms of graphene-based materials-induced programmed cell death: a review of apoptosis, autophagy, and programmed necrosis. Int J Nanomedicine. 2017;12:6633–46. https://doi.org/10.2147/IJN.S140526.10.2147/IJN.S140526 ↗
60. Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, et al. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ. 2012;19:107–20. https://doi.org/10.1038/cdd.2011.96.10.1038/cdd.2011.96 ↗
61. Green DR. Cell death in development. Cold Spring Harb Perspect Biol. 2020;14:1–3. https://doi.org/10.1101/cshperspect.a041095.10.1101/cshperspect.a041095 ↗
62. Liu B, Zhou H, Tan L, Siu KTH, Guan XY. Exploring treatment options in cancer: tumor treatment strategies. Signal Transduct Target Ther. 2024. https://doi.org/10.1038/s41392-024-01856-7.10.1038/s41392-024-01856-7 ↗
63. Vetrivel P, Kim SM, Saralamma VVG, Ha SE, Kim EH, Min TS, et al. Function of flavonoids on different types of programmed cell death and its mechanism: a review. J Biomed Res. 2019;33:363–70. https://doi.org/10.7555/JBR.33.20180126.10.7555/JBR.33.20180126 ↗
64. Zafar A, Khatoon S, Khan MJ, Abu J, Naeem A. Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy. Discov Oncol. 2025. https://doi.org/10.1007/s12672-025-02198-8.10.1007/s12672-025-02198-8 ↗
65. Hazafa A, Rehman KU, Jahan N, Jabeen Z. The role of polyphenol (flavonoids) compounds in the treatment of cancer cells. Nutr Cancer. 2020;72:386–97. https://doi.org/10.1080/01635581.2019.1637006.10.1080/01635581.2019.1637006 ↗