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Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study

Year 2026, Volume: 15 Issue: 1 , 174 - 181 , 30.03.2026
https://doi.org/10.46810/tdfd.1623422
https://izlik.org/JA45UC49DN

Abstract

This study was the first to evaluate the anticancer activity of doxorubicin -loaded niosomes on human brain cancer cells. Niosomal drug delivery systems were formulated using the thin film hydration method, incorporating Tween 40 and cholesterol in different ratios. The mean particle size, polydispersity index and zeta potential of empty niosomes were measured to be 150 nm, 0.265 and -21.5 mV, respectively. The loading efficiency of doxorubicin into the niosomes reached an impressive 95%. For doxorubicin-loaded niosomes, the mean particle size, polydispersity index and zeta potential were determined to be 174 nm, 0.290 and -22.8 mV, respectively. The drug release profile was assessed by UV-vis spectroscopy and showed a cumulative doxorubicin release of 30.8% over 24 hours. The cytotoxicity of doxorubicin-loaded niosomes was tested on healthy dermal fibroblast cells using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and showed no significant toxicity after 24 hours exposure to various concentrations. Conversely, significant anticancer effects were observed in SHSY-5Y and U87-MG brain cancer cell lines treated with doxorubicin-loaded niosomes, as evidenced by a significant decrease in cell proliferation compared to controls. Notably, the niosomal doxorubicin formulation exhibited higher anticancer efficacy compared to free doxorubicin. These results highlight the potential of niosomal drug delivery systems as a promising strategy to enhance the therapeutic efficacy of doxorubicin while minimizing its off-target toxicity.

References

  • Sarkar S, Horn G, Moulton K, Oza A, Byler S, Kokolus S, Longacre M. Cancer Development, Progression, and Therapy: An Epigenetic Overview. International Journal of Molecular Sciences. 2013; 14(10):21087-21113
  • Debela DT, Muzazu SGY, Heraro KD, Ndalama MT, Mesele BW, Haile DC, et al. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021 12:9:20503121211034366.
  • Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2014-2018. Neuro Oncol. 2021; 4;25(12 Suppl 2):iv1-iv99. doi: 10.1093/neuonc/noad149.
  • Sahu T, Ratre YK, Chauhan S, Bhaskar LVKS, Nair MP, Verma HK. Nanotechnology-based drug delivery system: Current strategies and emerging therapeutic potential for medical science. J Drug Deliv Sci Technol. 2021;63:102487.
  • Yasamineh S, Yasamineh P, Ghafouri Kalajahi H, Gholizadeh O, Yekanipour Z, Afkhami H, et al. A state-of-the-art review on the recent advances of niosomes as a targeted drug delivery system. Int J Pharm. 2022; 25:624:121878.
  • Pandey S, Tripathi P, Gupta A, Yadav JS. A comprehensive review on possibilities of treating psoriasis using dermal cyclosporine. Drug Deliv Transl Res. 2022;12(7): 1541-1555.
  • Durak S, Rad ME, Yetisgin AA, Sutova HE, Kutlu O, Cetinel S, et al. Niosomal drug delivery systems for ocular disease—recent advances and future prospects. Nanomaterials. 2020;10(6):1191.
  • Yıldırım ÖÇ, Arslan ME, Öner S, Cacciatore I, Di Stefano A, Mardinoglu A, et al. Boron nitride nanoparticles loaded with a boron-based hybrid as a promising drug carrier system for Alzheimer’s disease treatment. Int J Mol Sci. 2022;23(15):8249.
  • Faheela MK, Malathi S, Monica Susai Mary S, Narayana Kalkura S. In-vitro characterization of pluronic P123 based niosome for targeted delivery of doxorubicin. Mater Today Proc. 2022; 58:795–801
  • Türkez H, Yıldırım ÖÇ, Öner S, Kadı A, Mete A, Arslan ME, et al. Lipoic acid conjugated boron hybrids enhance wound healing and antimicrobial processes. Pharmaceutics. 2023;15(1):149.
  • Arslan ME. Anticarcinogenic properties of malic acid on glioblastoma cell line through necrotic cell death mechanism. MANAS J Eng. 2021;9(1):22-29.
  • Azmin MN, Florence AT, Handjani-Vila RM, Stuart JFB, Vanlerberghe G, Whittaker JS. The effect of non-ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice. J Pharm Pharmacol. 1985;37(4):237-242.
  • Zhu X, Yu Z, Feng L, Deng L, Fang Z, Liu Z, et al. Chitosan-based nanoparticle co-delivery of docetaxel and curcumin ameliorates anti-tumor chemoimmunotherapy in lung cancer. Carbohydr Polym. 2021; 268:118237.
  • Gharbavi M, Amani J, Kheiri-Manjili H, Danafar H, Sharafi A. Niosome: A promising nanocarrier for natural drug delivery through blood-brain barrier. Adv Pharmacol Sci. 2018;11: 6847971.
  • Mabrouk M, Das DB, Salem ZA, Beherei HH. Nanomaterials for Biomedical Applications: Production, Characterisations, Recent Trends and Difficulties. Molecules. 2021;26(4):1077.
  • Moammeri A, Chegeni MM, Sahrayi H, Ghafelehbashi R, Memarzadeh F, Mansouri A, Akbarzadeh I, Abtahi MS, Hejabi F, Ren Q. Current advances in niosomes applications for drug delivery and cancer treatment. Mater Today Bio. 2023 Oct 21;23:100837.
  • Khan R, Irchhaiya R. Niosomes: A potential tool for novel drug delivery. J Pharm Investig. 2016;46(3):195-204.
  • Karim K, Mandal A, Biswas N, Guha A, Chatterjee S, Behera M, et al. Niosome: A future of targeted drug delivery systems. J Adv Pharm Technol Res. 2010;1(4):374-380.
  • Burrini N, D’Ambrosio M, Gentili M, Giaquinto R, Settimelli V, Luceri C, et al. Niosomes functionalized with a synthetic carbohydrate binding agent for mannose-targeted doxorubicin delivery. Pharmaceutics. 2023;15(1):235.
  • Sharma V, Anandhakumar S, Sasidharan M. Self-degrading niosomes for encapsulation of hydrophilic and hydrophobic drugs: An efficient carrier for cancer multi-drug delivery. Mater Sci Eng C. 2015; 1:56:393-400.
  • Xu H, Xu X, Li S, Song WL, Yu DG, Bligh SWA. The effect of drug heterogeneous distributions within core-sheath nanostructures on its sustained release profiles. Biomolecules. 2021; 11(9):1330.
  • Targhi AA, Moammeri A, Jamshidifar E, Abbaspour K, Sadeghi S, Lamakani L, et al. Synergistic effect of curcumin-Cu and curcumin-Ag nanoparticle loaded niosome: Enhanced antibacterial and anti-biofilm activities. Bioorg Chem. 2021; 115:105116.
  • Esmaeili Rad M, Egil AC, Ozaydin Ince G, Yuce M, Zarrabi A. Optimization of curcumin loaded niosomes for drug delivery applications. Colloids Surf A Physicochem Eng Asp. 2022; 654(1):129921.
  • Sahab-Negah S, Ariakia F, Jalili-Nik M, Afshari AR, Salehi S, Samini F, et al. Curcumin loaded in niosomal nanoparticles improved the anti-tumor effects of free curcumin on glioblastoma stem-like cells: An in vitro study. Mol Neurobiol. 2020; 57(8):3391-3411.
  • Hemati M, Haghiralsadat F, Yazdian F, Jafari F, Moradi A, Malekpour-Dehkordi Z. Development and characterization of a novel cationic PEGylated niosome-encapsulated forms of doxorubicin, quercetin and siRNA for the treatment of cancer by using combination therapy. Artif Cells Nanomed Biotechnol. 2019; 47(1):1295-1311.
  • Uchegbu IF, Double JA, Kelland LR, Turton JA, Florence AT. The activity of doxorubicin niosomes against an ovarian cancer cell line and three in vivo mouse tumour models. J Drug Target. 1996; 3(5):399-409.
  • Basheer HA, Alhusban MA, Zaid Alkilani A, Alshishani A, Elsalem L, Afarinkia K. Niosomal delivery of celecoxib and metformin for targeted breast cancer treatment. Cancers (Basel). 2023; 15(20):5004.
  • Hoffmann LF, Martins A, Majolo F, Contini V, Laufer S, Goettert MI. Neural regeneration research model to be explored: SH-SY5Y human neuroblastoma cells. Neural Regen Res. 2023;18 (6):1265-1266.
  • Pilco-Ferreto N, Calaf GM. Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines. Int J Oncol. 2016;49(2):753-762.
  • Persano F, Gigli G, Leporatti S. Natural compounds as promising adjuvant agents in the treatment of gliomas. Int J Mol Sci. 2022; 23(6):3360.
  • Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: Role of ATP-dependent transporters. Nat Rev Cancer. 2002;2(1):48-58.
  • Anand U, Mukherjee S. Binding, unfolding and refolding dynamics of serum albumins. Biochim Biophys Acta Gen Subj. 2013;1830(12):5394-5404.
  • Malhotra M, Tomaro-Duchesneau C, Saha S, Kahouli I, Prakash S. Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA. Int J Nanomedicine. 2013;8:2041-2052.
  • Barani M, Mirzaei M, Torkzadeh-Mahani M, Lohrasbi-Nejad A, Nematollahi MH. A new formulation of hydrophobin-coated niosome as a drug carrier to cancer cells. Mater Sci Eng C. 2020;113:110975.

Doksorubisin Yüklü Niyozomal Taşıyıcılar Beyin Kanseri Hücrelerine Karşı Geliştirilmiş Sitotoksisite Sergiler: İn Vitro Bir Çalışma

Year 2026, Volume: 15 Issue: 1 , 174 - 181 , 30.03.2026
https://doi.org/10.46810/tdfd.1623422
https://izlik.org/JA45UC49DN

Abstract

Bu çalışma, doksorubisin yüklü niyozomların insan beyin kanseri hücreleri üzerindeki antikanser aktivitesini değerlendiren ilk çalışmadır. Farklı oranlarda Tween 40 ve kolesterol içeren niozomal ilaç taşıyıcıları ince film hidrasyon yöntemi kullanılarak formüle edilmiştir. Boş niyozomların ortalama partikül boyutu, polidispersite indeksi ve zeta potansiyeli sırasıyla 150 nm, 0.265 ve -21.5 mV olarak ölçülmüştür. Doksorubisinin niyozomlara yükleme etkinliği etkileyici bir şekilde %95'e ulaşmıştır. Doksorubisin yüklü niyozomlar için ortalama partikül boyutu, polidispersite indeksi ve zeta potansiyeli sırasıyla 174 nm, 0,290 ve -22,8 mV olarak belirlenmiştir. İlaç salım profili UV-vis spektroskopisi ile değerlendirilmiş ve 24 saat boyunca %30,8'lik kümülatif doksorubisin salımı göstermiştir. Doksorubisin yüklü niozomların sitotoksisitesi, sağlıklı dermal fibroblast hücreleri üzerinde 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür testi kullanılarak test edilmiş ve çeşitli konsantrasyonlara 24 saat maruz kaldıktan sonra önemli bir toksisite göstermemiştir.

References

  • Sarkar S, Horn G, Moulton K, Oza A, Byler S, Kokolus S, Longacre M. Cancer Development, Progression, and Therapy: An Epigenetic Overview. International Journal of Molecular Sciences. 2013; 14(10):21087-21113
  • Debela DT, Muzazu SGY, Heraro KD, Ndalama MT, Mesele BW, Haile DC, et al. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021 12:9:20503121211034366.
  • Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2014-2018. Neuro Oncol. 2021; 4;25(12 Suppl 2):iv1-iv99. doi: 10.1093/neuonc/noad149.
  • Sahu T, Ratre YK, Chauhan S, Bhaskar LVKS, Nair MP, Verma HK. Nanotechnology-based drug delivery system: Current strategies and emerging therapeutic potential for medical science. J Drug Deliv Sci Technol. 2021;63:102487.
  • Yasamineh S, Yasamineh P, Ghafouri Kalajahi H, Gholizadeh O, Yekanipour Z, Afkhami H, et al. A state-of-the-art review on the recent advances of niosomes as a targeted drug delivery system. Int J Pharm. 2022; 25:624:121878.
  • Pandey S, Tripathi P, Gupta A, Yadav JS. A comprehensive review on possibilities of treating psoriasis using dermal cyclosporine. Drug Deliv Transl Res. 2022;12(7): 1541-1555.
  • Durak S, Rad ME, Yetisgin AA, Sutova HE, Kutlu O, Cetinel S, et al. Niosomal drug delivery systems for ocular disease—recent advances and future prospects. Nanomaterials. 2020;10(6):1191.
  • Yıldırım ÖÇ, Arslan ME, Öner S, Cacciatore I, Di Stefano A, Mardinoglu A, et al. Boron nitride nanoparticles loaded with a boron-based hybrid as a promising drug carrier system for Alzheimer’s disease treatment. Int J Mol Sci. 2022;23(15):8249.
  • Faheela MK, Malathi S, Monica Susai Mary S, Narayana Kalkura S. In-vitro characterization of pluronic P123 based niosome for targeted delivery of doxorubicin. Mater Today Proc. 2022; 58:795–801
  • Türkez H, Yıldırım ÖÇ, Öner S, Kadı A, Mete A, Arslan ME, et al. Lipoic acid conjugated boron hybrids enhance wound healing and antimicrobial processes. Pharmaceutics. 2023;15(1):149.
  • Arslan ME. Anticarcinogenic properties of malic acid on glioblastoma cell line through necrotic cell death mechanism. MANAS J Eng. 2021;9(1):22-29.
  • Azmin MN, Florence AT, Handjani-Vila RM, Stuart JFB, Vanlerberghe G, Whittaker JS. The effect of non-ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice. J Pharm Pharmacol. 1985;37(4):237-242.
  • Zhu X, Yu Z, Feng L, Deng L, Fang Z, Liu Z, et al. Chitosan-based nanoparticle co-delivery of docetaxel and curcumin ameliorates anti-tumor chemoimmunotherapy in lung cancer. Carbohydr Polym. 2021; 268:118237.
  • Gharbavi M, Amani J, Kheiri-Manjili H, Danafar H, Sharafi A. Niosome: A promising nanocarrier for natural drug delivery through blood-brain barrier. Adv Pharmacol Sci. 2018;11: 6847971.
  • Mabrouk M, Das DB, Salem ZA, Beherei HH. Nanomaterials for Biomedical Applications: Production, Characterisations, Recent Trends and Difficulties. Molecules. 2021;26(4):1077.
  • Moammeri A, Chegeni MM, Sahrayi H, Ghafelehbashi R, Memarzadeh F, Mansouri A, Akbarzadeh I, Abtahi MS, Hejabi F, Ren Q. Current advances in niosomes applications for drug delivery and cancer treatment. Mater Today Bio. 2023 Oct 21;23:100837.
  • Khan R, Irchhaiya R. Niosomes: A potential tool for novel drug delivery. J Pharm Investig. 2016;46(3):195-204.
  • Karim K, Mandal A, Biswas N, Guha A, Chatterjee S, Behera M, et al. Niosome: A future of targeted drug delivery systems. J Adv Pharm Technol Res. 2010;1(4):374-380.
  • Burrini N, D’Ambrosio M, Gentili M, Giaquinto R, Settimelli V, Luceri C, et al. Niosomes functionalized with a synthetic carbohydrate binding agent for mannose-targeted doxorubicin delivery. Pharmaceutics. 2023;15(1):235.
  • Sharma V, Anandhakumar S, Sasidharan M. Self-degrading niosomes for encapsulation of hydrophilic and hydrophobic drugs: An efficient carrier for cancer multi-drug delivery. Mater Sci Eng C. 2015; 1:56:393-400.
  • Xu H, Xu X, Li S, Song WL, Yu DG, Bligh SWA. The effect of drug heterogeneous distributions within core-sheath nanostructures on its sustained release profiles. Biomolecules. 2021; 11(9):1330.
  • Targhi AA, Moammeri A, Jamshidifar E, Abbaspour K, Sadeghi S, Lamakani L, et al. Synergistic effect of curcumin-Cu and curcumin-Ag nanoparticle loaded niosome: Enhanced antibacterial and anti-biofilm activities. Bioorg Chem. 2021; 115:105116.
  • Esmaeili Rad M, Egil AC, Ozaydin Ince G, Yuce M, Zarrabi A. Optimization of curcumin loaded niosomes for drug delivery applications. Colloids Surf A Physicochem Eng Asp. 2022; 654(1):129921.
  • Sahab-Negah S, Ariakia F, Jalili-Nik M, Afshari AR, Salehi S, Samini F, et al. Curcumin loaded in niosomal nanoparticles improved the anti-tumor effects of free curcumin on glioblastoma stem-like cells: An in vitro study. Mol Neurobiol. 2020; 57(8):3391-3411.
  • Hemati M, Haghiralsadat F, Yazdian F, Jafari F, Moradi A, Malekpour-Dehkordi Z. Development and characterization of a novel cationic PEGylated niosome-encapsulated forms of doxorubicin, quercetin and siRNA for the treatment of cancer by using combination therapy. Artif Cells Nanomed Biotechnol. 2019; 47(1):1295-1311.
  • Uchegbu IF, Double JA, Kelland LR, Turton JA, Florence AT. The activity of doxorubicin niosomes against an ovarian cancer cell line and three in vivo mouse tumour models. J Drug Target. 1996; 3(5):399-409.
  • Basheer HA, Alhusban MA, Zaid Alkilani A, Alshishani A, Elsalem L, Afarinkia K. Niosomal delivery of celecoxib and metformin for targeted breast cancer treatment. Cancers (Basel). 2023; 15(20):5004.
  • Hoffmann LF, Martins A, Majolo F, Contini V, Laufer S, Goettert MI. Neural regeneration research model to be explored: SH-SY5Y human neuroblastoma cells. Neural Regen Res. 2023;18 (6):1265-1266.
  • Pilco-Ferreto N, Calaf GM. Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines. Int J Oncol. 2016;49(2):753-762.
  • Persano F, Gigli G, Leporatti S. Natural compounds as promising adjuvant agents in the treatment of gliomas. Int J Mol Sci. 2022; 23(6):3360.
  • Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: Role of ATP-dependent transporters. Nat Rev Cancer. 2002;2(1):48-58.
  • Anand U, Mukherjee S. Binding, unfolding and refolding dynamics of serum albumins. Biochim Biophys Acta Gen Subj. 2013;1830(12):5394-5404.
  • Malhotra M, Tomaro-Duchesneau C, Saha S, Kahouli I, Prakash S. Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA. Int J Nanomedicine. 2013;8:2041-2052.
  • Barani M, Mirzaei M, Torkzadeh-Mahani M, Lohrasbi-Nejad A, Nematollahi MH. A new formulation of hydrophobin-coated niosome as a drug carrier to cancer cells. Mater Sci Eng C. 2020;113:110975.
There are 34 citations in total.

Details

Primary Language English
Subjects Cell Development, Proliferation and Death
Journal Section Research Article
Authors

Özge Çağlar Yıldırım 0000-0003-1412-8411

Submission Date January 21, 2025
Acceptance Date February 10, 2026
Publication Date March 30, 2026
DOI https://doi.org/10.46810/tdfd.1623422
IZ https://izlik.org/JA45UC49DN
Published in Issue Year 2026 Volume: 15 Issue: 1

Cite

APA Yıldırım, Ö. Ç. (2026). Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study. Türk Doğa Ve Fen Dergisi, 15(1), 174-181. https://doi.org/10.46810/tdfd.1623422
AMA 1.Yıldırım ÖÇ. Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study. TJNS. 2026;15(1):174-181. doi:10.46810/tdfd.1623422
Chicago Yıldırım, Özge Çağlar. 2026. “Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study”. Türk Doğa Ve Fen Dergisi 15 (1): 174-81. https://doi.org/10.46810/tdfd.1623422.
EndNote Yıldırım ÖÇ (March 1, 2026) Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study. Türk Doğa ve Fen Dergisi 15 1 174–181.
IEEE [1]Ö. Ç. Yıldırım, “Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study”, TJNS, vol. 15, no. 1, pp. 174–181, Mar. 2026, doi: 10.46810/tdfd.1623422.
ISNAD Yıldırım, Özge Çağlar. “Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study”. Türk Doğa ve Fen Dergisi 15/1 (March 1, 2026): 174-181. https://doi.org/10.46810/tdfd.1623422.
JAMA 1.Yıldırım ÖÇ. Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study. TJNS. 2026;15:174–181.
MLA Yıldırım, Özge Çağlar. “Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study”. Türk Doğa Ve Fen Dergisi, vol. 15, no. 1, Mar. 2026, pp. 174-81, doi:10.46810/tdfd.1623422.
Vancouver 1.Özge Çağlar Yıldırım. Doxorubicin-Loaded Niosomal Transporters Demonstrate Enhanced Cytotoxicity Against Brain Cancer Cells: An In Vitro Study. TJNS. 2026 Mar. 1;15(1):174-81. doi:10.46810/tdfd.1623422

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