Synthesis of a stimuli-sensitive PEGylated nanoniosomal doxorubicin for the treatment of acute myeloid leukemia: An in vitro study

Document Type : Research Paper

Authors

1 Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Science, Yazd, Iran

2 Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Orthopedic Surgery, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

Abstract

Objective(s): One of the effective strategies for targeted chemotherapy of cancer is the use of lipid nanocarriers. In this study, an optimal formulation of niosomal drug containing doxorubicin was developed to monitor the potency against cancer cells. 
Materials and Methods: In this experimental study, niosomal vesicles were prepared using phosphatidylcholine (20%), span60 (52.5%), cholesterol (22.5%), and DSPE-PEG2000 (5%) by the thin-film method. Doxorubicin was loaded into the niosomes using an inactive loading method. 
Results: The features and characteristics of the nanocarrier were evaluated using Zeta-Sizer, SEM, FTIR, drug release, cellular uptake, and the cytotoxicity of the nanodrug carrier system by the MTT method. Niosomal vesicles-containing doxorubicin showed a size of ~156.8 nm, drug encapsulation efficiency of ~94.18%, zeta potential of ~-3.52 mV, and polydispersity index (PDI) of ~0.265. The prepared niosomes indicated a drug-controlled release system and FTIR analysis showed no interaction between nanocarriers containing drug and doxorubicin. Moreover, morphological examination of nanocarriers using SEM microscopy revealed that they had spherical structures. Also, cellular studies showed that drug toxicity was higher in encapsulated form of the drug compared with non-encapsulated doxorubicin which was confirmed by the cellular uptake results. 
Conclusion: The results confirmed the proper physicochemical characteristics of these nanocarriers that significantly increased the toxicity of the encapsulated drug against the KG-1 cell line. It seems niosomal nanocarriers can be considered suitable carriers for drug delivery to cancer cells.

Keywords

References

1.    Haghiralsadat F, Amoabediny G, Naderinezhad S, Zandieh-Doulabi B, Forouzanfar T, Helder MN. Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance. Int J Nanomedicine. 2018;13:3853.
2.    Haghiralsadat F, Amoabediny G, Naderinezhad S, Forouzanfar T, Helder MN, Zandieh-Doulabi B. Preparation of PEGylated cationic nanoliposome-siRNA complexes for cancer therapy. Artif Cells Nanomed.Biotechnol. 2018;46(sup1):684-692.
3.    Khatibi SA, Misaghi A, Moosavy MH, Basti AA, Koohi MK, Khosravi P, et al. Encapsulation of Zataria multiflora bioss. Essential oil into nanoliposomes and in vitro antibacterial activity against escherichia coli O157: H7. J Food Process Preserv. 2017;41(3):e12955.
4.    Askari E, Naghib SM, Seyfoori A, Maleki A, Rahmanian M. Ultrasonic-assisted synthesis and in vitro biological assessments of a novel herceptin-stabilized graphene using three dimensional cell spheroid. Ultrason Sonochem. 2019;58:104615.
5.    Pashazadeh-Panahi P, Belali S, Sohrabi H, Oroojalian F, Hashemzaei M, Mokhtarzadeh A, et al. Metal-organic frameworks conjugated with biomolecules as efficient platforms for development of biosensors. TrAC, Trends Anal Chem. 2021;141:116285.
6.    Rashidi A, Omidi M, Choolaei M, Nazarzadeh M, Yadegari A, Haghierosadat F, et al., editors. Electromechanical properties of vertically aligned carbon nanotube. Adv Mat Res; 2013: Trans Tech Publ.
7.    Fazaeli D, Mehrara R, Oroojalian F. Comparative efficacy of titanium dioxide nanoparticles loaded carboxymethyl cellulose and hydrogen peroxide gel on tooth whitening: An in-vitro study. Nanomed J. 2022;9(2):147-155.
8.    Rahmanian M, Dehghan MM, Eini L, Naghib SM, Gholami H, Mohajeri SF, et al. Multifunctional gelatin–tricalcium phosphate porous nanocomposite scaffolds for tissue engineering and local drug delivery: in vitro and in vivo studies. J Taiwan Inst Chem Eng. 2019;101:214-220.
9.    Salahandish R, Ghaffarinejad A, Naghib SM, Majidzadeh-A K, Zargartalebi H, Sanati-Nezhad A. Nano-biosensor for highly sensitive detection of HER2 positive breast cancer. Biosens Bioelectron. 2018;117:104-111.
10.    Gooneh-Farahani S, Naimi-Jamal MR, Naghib SM. Stimuli-responsive graphene-incorporated multifunctional chitosan for drug delivery applications: a review. Expert Opin Drug Deliv. 2019;16(1):79-99.
11.    Azizi M, Tavana M, Farsi M, Oroojalian F. Yield performance of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W. Curt.: Fr.) P. Karst.(higher Basidiomycetes), using different waste materials as substrates. Int J Med Mushrooms. 2012;14(5).
12.    Li S, Mason C, Melnick A. Genetic and Epigenetic Heterogeneity in Acute Myeloid Leukemia. Curr Opin Genet Dev. 2016;36:100-106.
13.    Qu X, Wan C, Becker H-C, Zhong D, Zewail AH. The anticancer drug–DNA complex: Femtosecond primary dynamics for anthracycline antibiotics function. Proc Natl Acad Sci USA. 2001;98(25):14212-14217.
14.    Hijiya N, Ness KK, Ribeiro RC, Hudson MM. Acute Leukemia as a Secondary Malignancy in Children and Adolescents: Current Findings and Issues. Cancer. 2009;115(1):23-35.
15.    Hashemi M, Yadegari A, Yazdanpanah G, Omidi M, Jabbehdari S, Haghiralsadat F, et al. Normalization of doxorubicin release from graphene oxide: New approach for optimization of effective parameters on drug loading. Biotechnol Appl Biochem. 2017;64(3):433-442.
16.    Haghiralsadat F, Amoabediny G, Naderinezhad S, Nazmi K, De Boer JP, Zandieh-Doulabi B, et al. EphA2 targeted doxorubicin-nanoliposomes for osteosarcoma treatment. Pharm Res. 2017;34(12):2891-2900.
17.    Gindy ME, Prud’homme RK. Multifunctional nanoparticles for imaging, delivery and targeting in cancer therapy. Expert Opin Drug Deliv. 2009;6(8):865-878.
18.    Fernandez-Fernandez A, Manchanda R, McGoron AJ. Theranostic applications of nanomaterials in cancer: drug delivery, image-guided therapy, and multifunctional platforms. Appl Biochem Biotechnol. 2011;165(7-8):1628-51.
19.    Abdel-Rashid RS, Abd Allah FI, Hassan AA, Hashim FM. Design, optimization, and in-vivo hypoglycemic effect of nanosized Glibenclamide for inhalation delivery. J Liposome Res. 2020(just-accepted):1-35.
20.    Singh AP, Biswas A, Shukla A, Maiti P. Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles. Signal Transduct Target Ther. 2019;4(1):1-21.
21.    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.
22.    De A, Venkatesh N, Senthil M, Sanapalli BKR, Shanmugham R, Karri VVSR. Smart niosomes of temozolomide for enhancement of brain targeting. Nanomed J. 2018;5:1849543518805355.
23.    Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug delivery systems: an illustrated review. JCR. 2014;185:22-36.
24.    Kamboj S, Saini V, Bala S. Formulation and Characterization of Drug Loaded Nonionic Surfactant Vesicles (Niosomes) for Oral Bioavailability Enhancement. Sci World J. 2014;2014:8.
25.    Nazari-Vanani R, Karimian K, Azarpira N, Heli H. Capecitabine-loaded nanoniosomes and evaluation of anticancer efficacy. Artif Cells Nanomed Biotechnol. 2019;47(1):420-426.
26.    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):1535-1549.
27.    Mirzaei-Parsa MJ, Najafabadi MRH, Haeri A, Zahmatkeshan M, Ebrahimi SA, Pazoki-Toroudi H, et al. Preparation, characterization, and evaluation of the anticancer activity of Artemether-loaded Nano-Niosomes against breast cancer. Breast Cancer. 2020;27(2):243-251.
28.    Hurtado Y, Franco CA, Riazi M, Cortés FB. Improving the stability of nitrogen foams using silica nanoparticles coated with polyethylene glycol. J Mol Liq. 2020;300:112256.
29.    Xue Y, Dong B, Liu X, Wang F, Yang J, Liu D. Using selenium-conjugated polyethylene glycol to enhance the stability of gold nanoparticles in biologically relevant samples. Sci China Chem. 2019;62(2):280-286.
30.    Khosravi A, Baharifar H, Darvishi MH, Zarchi AAK. Investigation of chitosan-g-PEG grafted nanoparticles as a half-life enhancer carrier for tissue plasminogen activator delivery. IET Nanobiotechnol. 2020.
31.    Shen C, Bian L, Zhang P, An B, Cui Z, Wang H, et al. Microstructure evolution of bonded water layer and morphology of grafting membrane with different polyethylene glycol length and their influence on permeability and anti-fouling capacity. J Membr Sci. 2020;601:117949.
32.    Kostenko MO, Pokrovskiy OI, Zakhodyaeva YA, Voshkin AA, Lunin VV. Unusual effect of flow rate on retention in analytical supercritical fluid chromatography exemplified by polyethylene glycol separation. J Chromatogr A. 2020;1610:460513.
33.    Baharifar H, Khoobi M, Arbabi Bidgoli S, Amani A. Preparation of PEG-grafted chitosan/streptokinase nanoparticles to improve biological half-life and reduce immunogenicity of the enzyme. Int J Biol Macromol. 2020;143:181-189.
34.    d’Avanzo N, Celia C, Barone A, Carafa M, Di Marzio L, Santos HA, et al. Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach. Adv Ther. 2020;3(3):1900170.
35.    Kim JY, Kim JK, Park JS, Byun Y, Kim CK. The use of PEGylated liposomes to prolong circulation lifetimes of tissue plasminogen activator. Biomaterials. 2009;30(29):5751-5756.
36.    Pishavar E, Oroojalian F, Ramezani M, Hashemi M. Cholesterol‐conjugated PEGylated PAMAM as an efficient nanocarrier for plasmid encoding interleukin‐12 immunogene delivery toward colon cancer cells. Biotechnol Prog. 2020;36(3):e2952.
37.    Gholami Z, Dadmehr M, Jelodar NB, Hosseini M, Parizi AP. One-pot biosynthesis of CdS quantum dots through in vitro regeneration of hairy roots of Rhaphanus sativus L. and their apoptosis effect on MCF-7 and AGS cancerous human cell lines. Mater Res Express. 2020;7(1):015056.
38.    Karimi MA, Dadmehr M, Hosseini M, Korouzhdehi B, Oroojalian F. Sensitive detection of methylated DNA and methyltransferase activity based on the lighting up of FAM-labeled DNA quenched fluorescence by gold nanoparticles. RSC Adv. 2019;9(21):12063-12069.
39.    Ebrahimpour M, Akhlaghi M, Hemati M, Ghazanfary S, Shahriary S, Ghalekohneh SJ, et al. In vitro evaluation and comparison of anticancer, antimicrobial, and antifungal properties of thyme niosomes containing essential oil. Nanomed J. 2022;9(4).
40.    Akhlaghi M, Taebpour M, Sharafaldini M, Javani O, Haghiralsadat BF, Oroojalian F, et al. Fabrication, characterization and evaluation of anti-cancer and antibacterial properties of nanosystems containing Hedera Helix aqueous extracts. Nanomed J. 2022;9(1):43-56.
41.    Sekeres MA. Treatment of older adults with acute myeloid leukemia: state of the art and current perspectives. Haematologica. 2008;93(12):1769-1772.
42.    Orgel E, Zung L, Ji L, Finklestein J, Feusner J, Freyer DR. Early cardiac outcomes following contemporary treatment for childhood acute myeloid leukemia: a North American perspective. Pediatr Blood cancer. 2013;60(9):1528-1533.
43.    Ruckmani K, Sankar V. Formulation and Optimization of Zidovudine Niosomes. AAPS PharmSciTech. 2010;11(3):1119-1127.
44.    Guinedi AS, Mortada ND, Mansour S, Hathout RM. Preparation and evaluation of reverse-phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide. Int J Pharm. 2005;306(1-2):71-82.
45.    Che J, Okeke CI, Hu ZB, Xu J. DSPE-PEG: a distinctive component in drug delivery system. Curr Pharm Des. 2015;21(12):1598-1605.
46.    Hong MS, Lim SJ, Oh YK, Kim CK. pH-sensitive, serum-stable and long-circulating liposomes as a new drug delivery system. J Pharm Pharmacol. 2002;54(1):51-58.
47.    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. 2018:1-17.
Nanomedicine Journal
Volume 10, Issue 1
January 2023
Pages 77-84

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