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Preparation, characterization, and evaluation of the anticancer activity of artemether-loaded nano-niosomes against breast cancer

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Abstract

Background

The aim of this study was to develop nonionic surfactant vesicles (niosomes) as a promising nanocarrier to enhance the anticancer activity of artemether.

Methods

The niosomes were prepared by thin-film hydration method containing a mixture of Span, Tween and cholesterol (Chol) in different molar ratios. All formulations were characterized in terms of size, entrapment efficiency (%EE), release profile and morphology. The optimized niosomal formulation (F7), artemether and phosphate buffered saline (PBS) were intratumorally administrated to mice as the nano-niosome group, the free drug group and the control group, respectively (n = 4 per group). Tumor volume was measured during the 12-day experiment, then mice were sacrificed to evaluate the necrosis, angiogenesis, and cell proliferation of tumor tissues by H&E, CD34 and Ki-67 immunostaining, respectively.

Results

Both artemether and nano-niosome groups could decrease angiogenesis and proliferation of tumor cells. However, in nano-niosome group superior tumor necrosis and smaller tumor volume were observed compared to both artemether and control groups.

Conclusions

The niosomal formulation could be a promising carrier for breast cancer treatment.

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References

  1. Mahdavifar N, Ghoncheh M, Pakzad R, Momenimovahed Z, Salehiniya H. Epidemiology, incidence and mortality of bladder cancer and their relationship with the development index in the world. Asian Pac J Cancer Prev. 2016;17(1):381–6.

    PubMed  Google Scholar 

  2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E386386.

    CAS  PubMed  Google Scholar 

  3. Efferth T. Mechanistic perspectives for 1, 2, 4-trioxanes in anti-cancer therapy. Drug Resist Updates. 2005;8(1–2):85–97.

    CAS  Google Scholar 

  4. Nakase I, Lai H, Singh NP, Sasaki T. Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation. Int J Pharm. 2008;354(1–2):28–33.

    CAS  PubMed  Google Scholar 

  5. Farsam V, Hassan ZM, Zavaran-Hosseini A, Noori S, Mahdavi M, Ranjbar M. Antitumor and immunomodulatory properties of artemether and its ability to reduce CD4+ CD25+ FoxP3+ T reg cells in vivo. Int Immunopharmacol. 2011;11(11):1802–8.

    CAS  PubMed  Google Scholar 

  6. Ebrahimisadr P, Ghaffarifar F, Hassan ZM. In-vitro evaluation of antileishmanial activity and toxicity of artemether with focus on its apoptotic effect. Iran J Pharm Res. 2013;12(4):903.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Singh NP, Panwar VK. Case report of a pituitary macroadenoma treated with artemether. Integr Cancer Ther. 2006;5(4):391–4.

    PubMed  Google Scholar 

  8. Ag Seleci D, Seleci M, Walter J-G, Stahl F, Scheper T. Niosomes as nanoparticular drug carriers: fundamentals and recent applications. J Nanomater. 2016;2016:7372306. https://doi.org/10.1155/2016/7372306.

    Article  Google Scholar 

  9. Hao Y-M, Li K. Entrapment and release difference resulting from hydrogen bonding interactions in niosome. Int J Pharm. 2011;403(1–2):245–53.

    CAS  PubMed  Google Scholar 

  10. Li L-N, Zhang H-D, Yuan S-J, Yang D-X, Wang L, Sun Z-X. Differential sensitivity of colorectal cancer cell lines to artesunate is associated with expression of beta-catenin and E-cadherin. Eur J Pharmacol. 2008;588(1):1–8.

    CAS  PubMed  Google Scholar 

  11. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403–10.

    CAS  PubMed  Google Scholar 

  12. Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug delivery systems: an illustrated review. J Control Release. 2014;185:22–36.

    CAS  PubMed  Google Scholar 

  13. Laxmi M, Bhardwaj A, Mehta S, Mehta A. Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether. Artif Cells Nanomed Biotechnol. 2015;43(5):334–44.

    CAS  PubMed  Google Scholar 

  14. Aditya N, Patankar S, Madhusudhan B, Murthy R, Souto E. Arthemeter-loaded lipid nanoparticles produced by modified thin-film hydration: pharmacokinetics, toxicological and in vivo anti-malarial activity. Eur J Pharm Sci. 2010;40(5):448–55.

    CAS  PubMed  Google Scholar 

  15. Nnamani PO, Hansen S, Windbergs M, Lehr C-M. Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application. Int J Pharm. 2014;477(1–2):208–17.

    CAS  PubMed  Google Scholar 

  16. Parashar D, Murthy RSR. Development of artemether and lumefantrine co-loaded nanostructured lipid carriers: physicochemical characterization and in vivo antimalarial activity. Drug Deliv. 2016;23(1):123–9.

    CAS  PubMed  Google Scholar 

  17. Attama AA, Kenechukwu FC, Onuigbo EB, Nnamani PO, Obitte N, Finke JH, et al. Solid lipid nanoparticles encapsulating a fluorescent marker (coumarin 6) and antimalarials–artemether and lumefantrine: evaluation of cellular uptake and antimalarial activity. Eur J Nanomed. 2016;8(3):129–38.

    CAS  Google Scholar 

  18. Shah SMH, Ullah F, Khan S, Shah SMM, de Matas M, Hussain Z, et al. Smart nanocrystals of artemether: fabrication, characterization, and comparative in vitro and in vivo antimalarial evaluation. Drug Des Dev Ther. 2016;10:3837.

    CAS  Google Scholar 

  19. Chen H-J, Huang X-R, Zhou X-B, Zheng B-Y, Huang J-D. Potential sonodynamic anticancer activities of artemether and liposome-encapsulated artemether. Chem Commun. 2015;51(22):4681–4.

    CAS  Google Scholar 

  20. Li X-Y, Zhao Y, Sun M-G, Shi J-F, Ju R-J, Zhang C-X, et al. Multifunctional liposomes loaded with paclitaxel and artemether for treatment of invasive brain glioma. Biomaterials. 2014;35(21):5591–604.

    CAS  PubMed  Google Scholar 

  21. Shah PP, Mashru RC, Thakkar AR, Badhan AC. Effect of chitosan crosslinking on bitterness of artemether using response surface methodology. J Pharm Pharmacol. 2008;60(4):421–7.

    CAS  PubMed  Google Scholar 

  22. Bachhav AA. Proniosome: a novel non-ionic provesicules as potential drug carrier. Asian J Pharm. 2016;10(03):210–22.

    Google Scholar 

  23. Ruckmani K, Jayakar B, Ghosal S. Nonionic surfactant vesicles (niosomes) of cytarabine hydrochloride for effective treatment of leukemias: encapsulation, storage, and in vitro release. Drug Dev Ind Pharm. 2000;26(2):217–22.

    CAS  PubMed  Google Scholar 

  24. Ruckmani K, Sankar V. Formulation and optimization of zidovudine niosomes. AAPS PharmSciTech. 2010;11(3):1119–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kumbhar D, Wavikar P, Vavia P. Niosomal gel of lornoxicam for topical delivery: in vitro assessment and pharmacodynamic activity. AAPS PharmSciTech. 2013;14(3):1072–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Tavano L, Alfano P, Muzzalupo R, de Cindio B. Niosomes vs microemulsions: new carriers for topical delivery of capsaicin. Colloids Surf B. 2011;87(2):333–9.

    CAS  Google Scholar 

  27. Cho YH, Kim S, Bae EK, Mok C, Park J. Formulation of a cosurfactant-free o/w microemulsion using nonionic surfactant mixtures. J Food Sci. 2008;73(3):E115–E12121.

    CAS  PubMed  Google Scholar 

  28. Desai TR, Finlay WH. Nebulization of niosomal all-trans-retinoic acid: an inexpensive alternative to conventional liposomes. Int J Pharm. 2002;241(2):311–7.

    CAS  PubMed  Google Scholar 

  29. Junyaprasert VB, Singhsa P, Suksiriworapong J, Chantasart D. Physicochemical properties and skin permeation of Span 60/Tween 60 niosomes of ellagic acid. Int J Pharm. 2012;423(2):303–11.

    CAS  PubMed  Google Scholar 

  30. Jin Y, Wen J, Garg S, Liu D, Zhou Y, Teng L, et al. Development of a novel niosomal system for oral delivery of Ginkgo biloba extract. Int J Nanomed. 2013;8:421.

    Google Scholar 

  31. Hamishehkar H, Rahimpour Y, Kouhsoltani M. Niosomes as a propitious carrier for topical drug delivery. Expert Opin Drug Deliv. 2013;10(2):261–72.

    CAS  PubMed  Google Scholar 

  32. Wu Z-P, Gao C-W, Wu Y-G, Zhu Q-S, Chen Y, Liu X, et al. Inhibitive effect of artemether on tumor growth and angiogenesis in the rat C6 orthotopic brain gliomas model. Integr Cancer Ther. 2009;8(1):88–92.

    PubMed  Google Scholar 

  33. Alcântara DDFÁ, Ribeiro HF, Cardoso PCDS, Araújo TMT, Burbano RR, Guimarães AC, et al. In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100). J Appl Toxicol. 2013;33(2):151–6.

    PubMed  Google Scholar 

  34. Zhao X, Guo X, Yue W, Wang J, Yang J, Chen J. Artemether suppresses cell proliferation and induces apoptosis in diffuse large B cell lymphoma cells. Exp Ther Med. 2017;14(5):4083–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Luo J-W, Zhang T, Zhang Q, Cao X, Zeng X, Fu Y, et al. A novel injectable phospholipid gel co-loaded with doxorubicin and bromotetrandrine for resistant breast cancer treatment by intratumoral injection. Colloids Surf B. 2016;140:538–47.

    CAS  Google Scholar 

  36. Nowroozi F, Dadashzadeh S, Soleimanjahi H, Haeri A, Shahhosseini S, Javidi J, et al. Theranostic niosomes for direct intratumoral injection: marked enhancement in tumor retention and anticancer efficacy. Nanomedicine. 2018;13(17):2201–19.

    CAS  PubMed  Google Scholar 

  37. Wang J-W, Xu J-H, Li J, Zhao M-H, Zhang H-F, Liu D-C, et al. Improvement of the antitumor efficacy of intratumoral administration of cucurbitacin poly (lactic-co-glycolic acid) microspheres incorporated in in situ-forming sucrose acetate isobutyrate depots. J Pharm Sci. 2016;105(1):205–11.

    PubMed  Google Scholar 

  38. Almond BA, Hadba AR, Freeman ST, Cuevas BJ, York AM, Detrisac CJ, et al. Efficacy of mitoxantrone-loaded albumin microspheres for intratumoral chemotherapy of breast cancer. J Control Release. 2003;91(1–2):147–55.

    CAS  PubMed  Google Scholar 

  39. Fong Y, Chen C-H, Chen J-P. Intratumoral delivery of doxorubicin on folate-conjugated graphene oxide by in-situ forming thermo-sensitive hydrogel for breast cancer therapy. Nanomaterials. 2017;7(11):388.

    PubMed Central  Google Scholar 

  40. Mooney R, Weng Y, Garcia E, Bhojane S, Smith-Powell L, Kim SU, et al. Conjugation of pH-responsive nanoparticles to neural stem cells improves intratumoral therapy. J Control Release. 2014;191:82–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Chu X-Y, Huang W, Wang Y-L, Meng L-W, Chen L-Q, Jin M-J, et al. Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin–chitosan nanoparticles loading paclitaxel–cholesterol complex. Int J Nanomed. 2019;14:689.

    CAS  Google Scholar 

  42. Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, et al. Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neurooncol. 2011;103(2):317–24.

    PubMed  Google Scholar 

  43. Lu B, Sun L, Yan X, Ai Z, Xu J. Intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy: a new method of neoadjuvant chemotherapy for stage III unresectable non-small cell lung cancer. Med Oncol. 2015;32(1):345.

    PubMed  Google Scholar 

  44. Yang H, Deng A, Zhang J, Wang J, Lu B. Preparation, characterization and anticancer therapeutic efficacy of cisplatin-loaded niosomes. J Microencapsul. 2013;30(3):237–44.

    CAS  PubMed  Google Scholar 

  45. Agarwal S, Mohamed MS, Raveendran S, Rochani AK, Maekawa T, Kumar DS. Formulation, characterization and evaluation of morusin loaded niosomes for potentiation of anticancer therapy. RSC Adv. 2018;8(57):32621–366.

    CAS  Google Scholar 

  46. Kassem MA, El-Sawy HS, Abd-Allah FI, Abdelghany TM, Khalid M. Maximizing the therapeutic efficacy of imatinib mesylate–loaded niosomes on human colon adenocarcinoma using Box-Behnken design. J Pharm Sci. 2017;106(1):111–22.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are thankful to Ms Golnam Abbasinia, Reza Vahidi, and Ms Fariba Esmaeili for their valuable technical assistance. This project was supported by Iran University of Medical Sciences (IUMS), Grant no. 94-02-130-26174.

Author information

Authors and Affiliations

  1. Department of Medical Nanotechnology, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran

    Mohamad Javad Mirzaei-Parsa

  2. Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran

    Mohamad Javad Mirzaei-Parsa

  3. Department of Medical Nanotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Reza H. Najafabadi

  4. Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Azadeh Haeri

  5. Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Masoumeh Zahmatkeshan

  6. Celullar and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

    Masoumeh Zahmatkeshan

  7. Department of Pharmacology, School of Medicine, Iran University of Medical Science, Tehran, Iran

    Soltan Ahmad Ebrahimi

  8. Physiology Department and Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Hamidreza Pazoki-Toroudi

  9. Deputy of Research and Technology, School of Medicine, Iran University of Medical Sciences, Hemat Highway Next to Milad Tower, Tehran, 1449614535, Iran

    Moein Adel

  10. Department of Medical Nanotechnology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Moein Adel

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  1. Mohamad Javad Mirzaei-Parsa
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  2. Mohammad Reza H. Najafabadi
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Correspondence to Moein Adel.

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All procedures performed in this study involving animals were in accordance with the ethical standards of the Institution Ethics Committee by Iran University of Medical Sciences.

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Mirzaei-Parsa, M.J., Najafabadi, M.R.H., Haeri, A. et al. Preparation, characterization, and evaluation of the anticancer activity of artemether-loaded nano-niosomes against breast cancer. Breast Cancer 27, 243–251 (2020). https://doi.org/10.1007/s12282-019-01014-w

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  • DOI: https://doi.org/10.1007/s12282-019-01014-w

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