Skip to main content
SpringerLink
Log in

Design and optimization various formulations of PEGylated niosomal nanoparticles loaded with phytochemical agents: potential anti-cancer effects against human lung cancer cells

  • Article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Phytochemicals and their derivatives are good options to improve treatment efficiency in cancer patients. Artemisinin (ART) and metformin (MET) are widely used phytochemicals to treat various types of cancers. However, their application because of their dose-dependent side effects, and poor bioavailability brings several challenges. Niosome is a novel nanocarrier that is the best choice to encapsulate both lipophilic and hydrophilic drugs. In this study, we synthesized and characterized various formulations of PEGylated (polyethylene glycol) niosomal nanoparticles co-loaded with ART-MET and evaluated their anticancer effect on A549 lung cancer cells.

Methods

Various formulations of PEGylated noisome were prepared by the thin-film hydration method and characterized in size, morphology, release pattern, and physicochemical structure. The cytotoxic effect of the free ART-MET and optimized PEGylated niosomal nanoparticles loaded with ART-MET on A549 cells were evaluated by MTT assay. Furthermore, the Real-time PCR (RT-PCR) technique used to evaluate apoptotic and anti-apoptotic gene expression.

Results

The size, encapsulation efficiency (EE), and polydispersity index (PDI) of the optimized nanoparticles are 256 nm, 95%, and 0.202, respectively. Additionally, due to the PEGylation hydrophilic character, there is a major consideration of the high impact of PEGylation on reducing niosome size. According to the results of the MTT assay, free ART-MET and ART-MET-loaded niosomal nanoparticles showed dose-dependent toxicity and inhibits the growth of A549 lung cancer cells. Furthermore, the RT-PCR results indicated that ART-MET-loaded niosomal nanoparticles have a higher anti-proliferative effect by inhibiting anti-apoptotic and inducing apoptotic gene expression in A549 lung cancer cells.

Conclusions

Our study revealed that the simultaneous use of ART and MET in the optimized PEGylated niosomal nanoparticles delivery system could be an appropriate approach to improve the effectiveness of lung cancer treatment.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The data that support the findings of this study are included in the supplementary files.

Abbreviations

AFM:

Atomic force microscopy

ART:

Artemisinin

Chol:

Cholesterol

DLS:

Dynamic light scattering

EE:

Encapsulation efficiency

FBS:

Fetal bovine serum

FE-SEM:

Field emission scanning electron microscopes

MET:

Metformin

Nio:

Niosome

Nio-ART:

Niosome loaded artemisinin

Nio-MET:

Niosome loaded metformin

PBS:

Phosphate-buffered saline

PDI:

Polydispersity index

PEG:

Polyethylene glycol

TEM:

Transmission electron microscopy

TFH:

Thin-film hydration

WHO:

World health organization

ZP:

Zeta potential

References

  1. WH Organization. WHO report on cancer: setting priorities, investing wisely and providing care for all. Geneva: World Health Organization; 2020.

    Google Scholar 

  2. Shin H, Oh S, Hong S, Kang M, Kang D, Ji Y-g, et al. Early-stage lung cancer diagnosis by deep learning-based spectroscopic analysis of circulating exosomes. ACS Nano. 2020;14(5):5435–44.

    Article  CAS  PubMed  Google Scholar 

  3. Petrovic D, Bodinier B, Dagnino S, Whitaker M, Karimi M, Campanella G, et al. Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking. Eur J Epidemiol. 2022;37:1–12.

    Article  Google Scholar 

  4. Tran VV, Park D, Lee Y-C. Indoor air pollution, related human diseases, and recent trends in the control and improvement of indoor air quality. Int J Environ Health Res. 2020;17(8):2927.

    Article  Google Scholar 

  5. Willers H, Stinchcombe TE, Barriger RB, Chetty IJ, Ginsburg ME, Kestin LL, et al. ACR appropriateness criteria® induction and adjuvant therapy for N2 non–small-cell lung cancer. Am J Clin Oncol. 2015;38(2):197–205.

    Article  CAS  PubMed  Google Scholar 

  6. Travis WD. Pathology & genetics tumours of the lung, pleura, thymus and heart. World Health Organization classification of tumours. 2004;10(3):341

  7. Suster DI, Mino-Kenudson M. Molecular pathology of primary non-small cell lung cancer. Arch Med Res. 2020;51(8):784–98.

    Article  CAS  PubMed  Google Scholar 

  8. Minna JD, Roth JA, Gazdar AF. Focus on lung cancer. Cancer Cell. 2002;1(1):49–52.

    Article  CAS  PubMed  Google Scholar 

  9. Colby TV, Wistuba II, Gazdar A. Precursors to pulmonary neoplasia. Adv Anat Pathol. 1998;5(4):205–15.

    Article  CAS  PubMed  Google Scholar 

  10. Khazei K, Mohajeri N, Bonabi E, Turk Z, Zarghami N. New insights toward nanostructured drug delivery of plant-derived polyphenol compounds: cancer treatment and gene expression profiles. Curr Cancer Drug Targets. 2021;21(8):689–701.

    Article  CAS  PubMed  Google Scholar 

  11. Kong M, Xie K, Lv M, Li J, Yao J, Yan K, et al. Anti-inflammatory phytochemicals for the treatment of diabetes and its complications: Lessons learned and future promise. Biomed Pharmacother. 2021;133: 110975.

    Article  CAS  PubMed  Google Scholar 

  12. Khodadadi M, Jafari-Gharabaghlou D, Zarghami N. An update on mode of action of metformin in modulation of meta-inflammation and inflammaging. Pharmacol Rep. 2022;74:310–22.

    Article  CAS  PubMed  Google Scholar 

  13. Hassani N, Jafari-Gharabaghlou D, Dadashpour M, Zarghami N. The effect of dual bioactive compounds artemisinin and metformin co-loaded in PLGA-PEG nano-particles on breast cancer cell lines: potential apoptotic and anti-proliferative action. Appl Biochem Biotechnol. 2022;194:1–16.

    Article  Google Scholar 

  14. Ghasemali S, Nejati-Koshki K, Akbarzadeh A, Tafsiri E, Zarghami N, Rahmati-Yamchi M, et al. Inhibitory effects of β-cyclodextrin-helenalin complexes on H-TERT gene expression in the T47D breast cancer cell line-results of real time quantitative PCR. Asian Pac J Cancer Prev. 2013;14(11):6949–53.

    Article  PubMed  Google Scholar 

  15. Alibakhshi A, Ranjbari J, Pilehvar-Soltanahmadi Y, Nasiri M, Mollazade M, Zarghami N. An update on phytochemicals in molecular target therapy of cancer: potential inhibitory effect on telomerase activity. Curr Med Chem. 2016;23(22):2380–93.

    Article  CAS  PubMed  Google Scholar 

  16. Mohammadian F, Abhari A, Dariushnejad H, Nikanfar A, Pilehvar-Soltanahmadi Y, Zarghami N. Effects of chrysin-PLGA-PEG nanoparticles on proliferation and gene expression of miRNAs in gastric cancer cell line. Iran J Cancer Prev. 2016. https://doi.org/10.17795/ijcp-4190.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tavakoli F, Jahanban-Esfahlan R, Seidi K, Jabbari M, Behzadi R, Pilehvar-Soltanahmadi Y, et al. Effects of nano-encapsulated curcumin-chrysin on telomerase, MMPs and TIMPs gene expression in mouse B16F10 melanoma tumour model. Artif Cells Nanomed Biotechnol. 2018;46(sup2):75–86.

    Article  CAS  PubMed  Google Scholar 

  18. Slezáková S, Ruda-Kucerova J. Anticancer activity of artemisinin and its derivatives. Anticancer res. 2017;37(11):5995–6003.

    PubMed  Google Scholar 

  19. Jafari-Gharabaghlou D, Pilehvar-Soltanahmadi Y, Dadashpour M, Mota A, Vafajouy-Jamshidi S, Faramarzi L, et al. Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells. Iran J Basic Med Sci. 2018;21(11):1167.

    PubMed  PubMed Central  Google Scholar 

  20. Salmani Javan E, Lotfi F, Jafari-Gharabaghlou D, Mousazadeh H, Dadashpour M, Zarghami N. Development of a magnetic nanostructure for co-delivery of metformin and silibinin on growth of lung cancer cells: Possible action through leptin gene and its receptor regulation. Asian Pac J Cancer Prev. 2022;23(2):519–27.

    Article  PubMed  Google Scholar 

  21. Alagheband Y, Jafari-gharabaghlou D, Imani M, Mousazadeh H, Dadashpour M, Firouzi-Amandi A, et al. Design and fabrication of a dual-drug loaded nano-platform for synergistic anticancer and cytotoxicity effects on the expression of leptin in lung cancer treatment. J Drug Deliv Sci Technol. 2022;73: 103389.

    Article  CAS  Google Scholar 

  22. Javidfar S, Pilehvar-Soltanahmadi Y, Farajzadeh R, Lotfi-Attari J, Shafiei-Irannejad V, Hashemi M, et al. The inhibitory effects of nano-encapsulated metformin on growth and hTERT expression in breast cancer cells. J Drug Deliv Sci Technol. 2018;43:19–26.

    Article  CAS  Google Scholar 

  23. Wahdan-Alaswad RS, Thor AD. Metformin activity against breast cancer: mechanistic differences by molecular subtype and metabolic conditions. London: IntechOpen; 2020.

    Google Scholar 

  24. Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle. 2009;8(1):88–96.

    Article  CAS  PubMed  Google Scholar 

  25. Milewska S, Niemirowicz-Laskowska K, Siemiaszko G, Nowicki P, Wilczewska AZ, Car H. Current trends and challenges in pharmacoeconomic aspects of nanocarriers as drug delivery systems for cancer treatment. Int J Nanomed. 2021;16:6593.

    Article  Google Scholar 

  26. Zamani R, Aval SF, Pilehvar-Soltanahmadi Y, Nejati-Koshki K, Zarghami N. Recent advances in cell electrospining of natural and synthetic nanofibers for regenerative medicine. Drug res. 2018;68(08):425–35.

    Article  CAS  Google Scholar 

  27. Khan MI, Hossain MI, Hossain MK, Rubel M, Hossain K, Mahfuz A, et al. Recent progress in nanostructured smart drug delivery systems for cancer therapy: a review. ACS Appl Bio Mater. 2022;5(3):971–1012.

    Article  CAS  PubMed  Google Scholar 

  28. Akbarzadeh I, Keramati M, Azadi A, Afzali E, Shahbazi R, Norouzian D, et al. Optimization, physicochemical characterization, and antimicrobial activity of a novel simvastatin nano-niosomal gel against E. coli and S. aureus. Chem Phys Lipids. 2021;234:105019.

    Article  CAS  PubMed  Google Scholar 

  29. Akbarzadeh I, Saremi Poor A, Yaghmaei S, Norouzian D, Noorbazargan H, Saffar S, et al. Niosomal delivery of simvastatin to MDA-MB-231 cancer cells. Drug Dev Ind Pharm. 2020;46(9):1535–49.

    Article  CAS  PubMed  Google Scholar 

  30. Manosroi A, Khanrin P, Lohcharoenkal W, Werner RG, Götz F, Manosroi W, et al. Transdermal absorption enhancement through rat skin of gallidermin loaded in niosomes. Int J Pharm. 2010;392(1–2):304–10.

    Article  CAS  PubMed  Google Scholar 

  31. Mohawed OA, El-Ashmoony M, Elgazayerly ON. Niosome-encapsulated clomipramine for transdermal controlled delivery. Int J Pharm Pharm Sci. 2014;6(9):567–75.

    CAS  Google Scholar 

  32. Usama A, Fetih G, El-Faham T. Performance of meloxicam niosomal gel formulations for transdermal drug delivery. Br J Pharm Res. 2016;12(2):1–14.

    Article  Google Scholar 

  33. Azeem A, Ahmad FJ, Khan ZI, Talegaonkar S. Nonionic surfactant vesicles as a carrier for transdermal delivery of frusemide. J Dispers Sci Technol. 2008;29(5):723–30.

    Article  CAS  Google Scholar 

  34. Abdelkader H, Wu Z, Al-Kassas R, Alany RG. Niosomes and discomes for ocular delivery of naltrexone hydrochloride: morphological, rheological, spreading properties and photo-protective effects. Int J Pharm. 2012;433(1–2):142–8.

    Article  CAS  PubMed  Google Scholar 

  35. Zeng W, Li Q, Wan T, Liu C, Pan W, Wu Z, et al. Hyaluronic acid-coated niosomes facilitate tacrolimus ocular delivery: mucoadhesion, precorneal retention, aqueous humor pharmacokinetics, and transcorneal permeability. Coll Surf B Biointerfaces. 2016;141:28–35.

    Article  CAS  Google Scholar 

  36. Bansal S, Aggarwal G, Chandel P, Harikumar S. Design and development of cefdinir niosomes for oral delivery. J Pharm Bioallied Sci. 2013;5(4):318.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bini K, Akhilesh D, Prabhakara P, Kamath J. Development and characterization of non-ionic surfactant vesicles (niosomes) for oral delivery of lornoxicam. Int J Drug Dev Res. 2012;4(3):147–54.

    CAS  Google Scholar 

  38. Marianecci C, Paolino D, Celia C, Fresta M, Carafa M, Alhaique F. Non-ionic surfactant vesicles in pulmonary glucocorticoid delivery: characterization and interaction with human lung fibroblasts. J Control Release. 2010;147(1):127–35.

    Article  CAS  PubMed  Google Scholar 

  39. De A, Venkatesh N, Senthil M, Sanapalli BKR, Shanmugham R, Karri VVSR. Smart niosomes of temozolomide for enhancement of brain targeting. Nanobiomedicine. 2018;5:1849543518805355.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Abdelkader H, Alani AW, Alany RG. Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations. Drug deliv. 2014;21(2):87–100.

    Article  CAS  PubMed  Google Scholar 

  41. Azmin M, Florence A, Handjani-Vila R, Stuart J, Vanlerberghe G, Whittaker J. The effect of non-ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice. J Pharm Pharmacol. 1985;37(4):237–42.

    Article  CAS  PubMed  Google Scholar 

  42. Jain C, Vyas S, Dixit V. Niosomal system for delivery of rifampicin to lymphatics. Indian J Pharm Sci. 2006;68(5):575.

    Article  CAS  Google Scholar 

  43. Ansari MJ, Anwer MK, Jamil S, Al-Shdefat R, Ali BE, Ahmad MM, et al. Enhanced oral bioavailability of insulin-loaded solid lipid nanoparticles: pharmacokinetic bioavailability of insulin-loaded solid lipid nanoparticles in diabetic rats. Drug Deliv. 2016;23(6):1972–9.

    CAS  PubMed  Google Scholar 

  44. Ghafelehbashi R, Akbarzadeh I, Yaraki MT, Lajevardi A, Fatemizadeh M, Saremi LH. Preparation, physicochemical properties, in vitro evaluation and release behavior of cephalexin-loaded niosomes. Int J Pharm. 2019;569: 118580.

    Article  CAS  PubMed  Google Scholar 

  45. Nasseri B. Effect of cholesterol and temperature on the elastic properties of niosomal membranes. Int J Pharm. 2005;300(1–2):95–101.

    Article  CAS  PubMed  Google Scholar 

  46. Mehta SK, Jindal N, Kaur G. Quantitative investigation, stability and in vitro release studies of anti-TB drugs in triton niosomes. Coll Surf B Biointerfaces. 2011;87(1):173–9.

    Article  CAS  Google Scholar 

  47. Shafiei-Irannejad V, Samadi N, Yousefi B, Salehi R, Velaei K, Zarghami N. Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P-gp-overexpressing MCF-7 cells. Chem Biol Drug Des. 2018;91(1):269–76.

    Article  CAS  PubMed  Google Scholar 

  48. Eatemadi A, Daraee H, Aiyelabegan HT, Negahdari B, Rajeian B, Zarghami N. Synthesis and characterization of chrysin-loaded PCL-PEG-PCL nanoparticle and its effect on breast cancer cell line. Biomed Pharmacother. 2016;84:1915–22.

    Article  CAS  PubMed  Google Scholar 

  49. Sadeghzadeh H, Pilehvar-Soltanahmadi Y, Akbarzadeh A, Dariushnejad H, Sanjarian F, Zarghami N. The effects of nanoencapsulated curcumin-Fe3O4 on proliferation and hTERT gene expression in lung cancer cells. Anti-Cancer Agents Med Chem. 2017;17(10):1363–73.

    Article  CAS  Google Scholar 

  50. Muzzalupo R, Tavano L. Niosomal drug delivery for transdermal targeting: recent advances. Res Rep Transdermal Drug Deliv. 2015;4:23–33.

    CAS  Google Scholar 

  51. Rochdy Haj-Ahmad R, Ali Elkordy A, Shu CC. In vitro characterisation of span™ 65 niosomal formulations containing proteins. Curr Drug Deliv. 2015;12(5):628–39.

    Article  PubMed  Google Scholar 

  52. Abdelkader H, Farghaly U, Moharram H. Effects of surfactant type and cholesterol level on niosomes physical properties and in vivo ocular performance using timolol maleate as a model drug. J Pharm Investig. 2014;44(5):329–37.

    Article  CAS  Google Scholar 

  53. Abdelkader H, Ismail S, Kamal A, Alany RG. Design and evaluation of controlled-release niosomes and discomes for naltrexone hydrochloride ocular delivery. J Pharm Sci. 2011;100(5):1833–46.

    Article  CAS  PubMed  Google Scholar 

  54. Li Q, Li Z, Zeng W, Ge S, Lu H, Wu C, et al. Proniosome-derived niosomes for tacrolimus topical ocular delivery: in vitro cornea permeation, ocular irritation, and in vivo anti-allograft rejection. Eur J Pharm Sci. 2014;62:115–23.

    Article  CAS  PubMed  Google Scholar 

  55. Basiri L, Rajabzadeh G, Bostan A. α-Tocopherol-loaded niosome prepared by heating method and its release behavior. Food chem. 2017;221:620–8.

    Article  CAS  PubMed  Google Scholar 

  56. Shaker DS, Shaker MA, Hanafy MS. Cellular uptake, cytotoxicity and in-vivo evaluation of tamoxifen citrate loaded niosomes. Int J Pharm. 2015;493(1–2):285–94.

    Article  CAS  PubMed  Google Scholar 

  57. 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.

    Article  CAS  PubMed  Google Scholar 

  58. Patel J, Ketkar S, Patil S, Fearnley J, Mahadik KR, Paradkar AR. Potentiating antimicrobial efficacy of propolis through niosomal-based system for administration. Integr Med Res. 2015;4(2):94–101.

    Article  PubMed  Google Scholar 

  59. Bragagni M, Mennini N, Furlanetto S, Orlandini S, Ghelardini C, Mura P. Development and characterization of functionalized niosomes for brain targeting of dynorphin-B. Eur J Pharm Biopharm. 2014;87(1):73–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  61. Husseini GA, De La Rosa MAD, Richardson ES, Christensen DA, Pitt WG. The role of cavitation in acoustically activated drug delivery. J Control Release. 2005;107(2):253–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Varshosaz J, Pardakhty A, Hajhashemi V-i, Najafabadi AR. Development and physical characterization of sorbitan monoester niosomes for insulin oral delivery. Drug Deliv. 2003;10(4):251–62.

    Article  CAS  PubMed  Google Scholar 

  63. Moazeni E, Gilani K, Sotoudegan F, Pardakhty A, Najafabadi AR, Ghalandari R, et al. Formulation and in vitro evaluation of ciprofloxacin containing niosomes for pulmonary delivery. J Microencapsul. 2010;27(7):618–27.

    Article  CAS  PubMed  Google Scholar 

  64. Marwa A, Omaima S, Hanaa E-G, Mohammed A-S. Preparation and in-vitro evaluation of diclofenac sodium niosomal formulations. Int J Pharm Sci Res. 2013;4(5):1757.

    Google Scholar 

  65. Richardson ES, Pitt WG, Woodbury DJ. The role of cavitation in liposome formation. Biophys J. 2007;93(12):4100–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Lee S-C, Lee K-E, Kim J-J, Lim S-H. The effect of cholesterol in the liposome bilayer on the stabilization of incorporated retinol. J Liposome Res. 2005;15(3–4):157–66.

    Article  CAS  PubMed  Google Scholar 

  67. Cable C. An examination of the effect of surface modifications on the physicochemical and biological properties of non-ionic surfactant vesicles (surfactant vesicles, physicochemical properties), in Ph. D. Thesis 1989. Strathclyde: Glasgow

  68. Patel H. Liposomes: a practical approach: edited by RRC New. Oxford: Oxford University Press; 1990. p. 301 (£ 22.50. No longer published by Elsevier; 1990).

    Google Scholar 

  69. Gupta M, Vaidya B, Mishra N, Vyas SP. Effect of surfactants on the characteristics of fluconazole niosomes for enhanced cutaneous delivery. Artif Cells Blood Substit Immobil Biotechnol. 2011;39(6):376–84.

    Article  CAS  PubMed  Google Scholar 

  70. Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm. 1998;172(1–2):33–70.

    Article  CAS  Google Scholar 

  71. Khazaeli P, Pardakhty A, Shoorabi H. Caffeine-loaded niosomes: characterization and in vitro release studies. Drug deliv. 2007;14(7):447–52.

    Article  CAS  PubMed  Google Scholar 

  72. Yoshioka T, Sternberg B, Florence AT. Preparation and properties of vesicles (niosomes) of sorbitan monoesters (Span 20, 40, 60 and 80) and a sorbitan triester (Span 85). Int J Pharm. 1994;105:1.

    Article  CAS  Google Scholar 

  73. Sadeghi S, Bakhshandeh H, Cohan RA, Peirovi A, Ehsani P, Norouzian D. Synergistic anti-staphylococcal activity of niosomal recombinant lysostaphin-LL-37. Int J Nanomed. 2019;14:9777.

    Article  CAS  Google Scholar 

  74. Barani M, Mirzaei M, Torkzadeh-Mahani M, Nematollahi MH. Lawsone-loaded niosome and its antitumor activity in MCF-7 breast cancer cell line: a nano-herbal treatment for cancer. DARU J Pharm Sci. 2018;26(1):11–7.

    Article  CAS  Google Scholar 

  75. Hajizadeh MR, Maleki H, Barani M, Fahmidehkar MA, Mahmoodi M, Torkzadeh-Mahani M. In vitro cytotoxicity assay of D-limonene niosomes: an efficient nano-carrier for enhancing solubility of plant-extracted agents. Res Pharm Sci. 2019;14(5):448.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Hao Y, Zhao F, Li N, Yang Y. Studies on a high encapsulation of colchicine by a niosome system. Int J Pharm. 2002;244(1–2):73–80.

    Article  CAS  PubMed  Google Scholar 

  77. Pardakhty A, Moazeni E, Varshosaz J, Hajhashemi V, Najafabadi AR. Pharmacokinetic study of niosome-loaded insulin in diabetic rats. DARU J Pharm Sci. 2011;19(6):404.

    CAS  Google Scholar 

  78. Akbarzadeh I, Yaraki MT, Bourbour M, Noorbazargan H, Lajevardi A, Shilsar SMS, et al. Optimized doxycycline-loaded niosomal formulation for treatment of infection-associated prostate cancer: an in-vitro investigation. J Drug Deliv Sci Technol. 2020;57: 101715.

    Article  CAS  Google Scholar 

  79. Seras-Cansell M, Ollivon M, Lesieur S. Generation of non-ionic monoalkyl amphiphile-cholesterol vesicles: evidence of membrane impermeability to octyl glucoside. STP Pharma Sci. 1996;6(1):12–20.

    Google Scholar 

  80. Yoon O, Roh J. Downregulation of KLF4 and the Bcl-2/Bax ratio in advanced epithelial ovarian cancer. Oncol Lett. 2012;4(5):1033–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Chen J, Zhang L, Hao M. Effect of artemisinin on proliferation and apoptosis-related protein expression in vivo and in vitro. Saudi J Biol Sci. 2018;25(7):1488–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the Tabriz University of Medical Sciences and Islamic Azad University Science and Research Branch of Tehran for all supporting and laboratory facilities for this study.

Funding

We thank the Tabriz University of Medical Sciences for all supporting.

Author information

Authors and Affiliations

  1. Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Rasoul Shahbazi & Zohreh Mirjafary

  2. Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Davoud Jafari-Gharabaghlou

  3. Department of Science, Payame Noor University (PNU), P.O. Box 19395-3697, Tehran, Iran

    Hamid Saeidian

  4. Tuberculosis and Lung Diseases Research Center, University of Medical Sciences, Tabriz, Iran

    Nosratollah Zarghami

  5. Department of Medical Biochemistry, Faculty of Medicine, Istanbul Aydin University, Istanbul, Turkey

    Nosratollah Zarghami

Authors
  1. Rasoul Shahbazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Davoud Jafari-Gharabaghlou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zohreh Mirjafary
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hamid Saeidian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nosratollah Zarghami
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RS: investigation, validation, methodology, data curation, writing—original draft. DJ-G: supervision, validation, writing—review and editing. ZM and HS: writing—review and editing. NZ: supervision, validation.

Corresponding author

Correspondence to Nosratollah Zarghami.

Ethics declarations

Conflict of interest

The authors declare there is no conflict of interest.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

43440_2023_462_MOESM1_ESM.docx

Supplementary file1 Table S1. Optimizing PEGylated-ART-MET-loaded niosomes by D-optimal design used by design expert 12.0.3.0 software. N: noisome, ART: artemisinin, MET: metformin, S: Surfactant type, A: The amount of surfactant (mM), B: The amount of cholesterol (mM), P: The amount of polyethylene glycol (mM), PDI: polydispersity index, EE: encapsulation efficiency (%). Results are presented as mean ± standard deviation; in all niosomal formulations, entrapment efficiency was significantly different from each other p <0.05 (DOCX 13 KB)

43440_2023_462_MOESM2_ESM.docx

Supplementary file2 Table S2. Various formulations of niosomal NPs. F: formulation. S: The amount of surfactant, Ch: The amount of cholesterol, HLB: hydrophilic-lipophilic balance, S/Ch: molar ratio of surfactant to cholesterol. Experiments were carried out three times and the results are presented as mean ± SD (n = 3) (DOCX 12 KB)

43440_2023_462_MOESM3_ESM.docx

Supplementary file3 Table S3. ART-MET-loaded niosomal NPs stability and changes in particle size (nm), entrapment efficiency (EE), and polydispersity index (PDI) at 4 ± 0.5 °c and 25 ± 1 °C during two months. Size (nm), PDI: polydispersity index, EE: entrapment efficiency (DOCX 12 KB)

Supplementary file4 (JPEG 36 KB)

Supplementary file5 (CSV 56 KB)

Supplementary file6 (XLSX 10 KB)

Supplementary file7 (XLSX 15 KB)

Supplementary file8 (XLSX 9 KB)

Supplementary file9 (CSV 52 KB)

Supplementary file10 (XLSX 10 KB)

Supplementary file11 (XLSX 10 KB)

Supplementary file12 (XLSX 15 KB)

Supplementary file13 (CSV 52 KB)

Supplementary file14 (XLSX 57 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shahbazi, R., Jafari-Gharabaghlou, D., Mirjafary, Z. et al. Design and optimization various formulations of PEGylated niosomal nanoparticles loaded with phytochemical agents: potential anti-cancer effects against human lung cancer cells. Pharmacol. Rep 75, 442–455 (2023). https://doi.org/10.1007/s43440-023-00462-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43440-023-00462-8

Keywords

Search

Navigation