Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Cytotoxicity of Chitosan Ultrafine Nanoshuttles on the MCF-7 Cell Line as a Surrogate Model for Breast Cancer

Author(s): Tarek Faris*, Gamaleldin I. Harisa, Fars K. Alanazi, Mohamed M. Badran, Afraa Mohammad Alotaibi, Hafsa Almanea, Ali S. Alqahtani and Ahmed M. Samy

Volume 18, Issue 1, 2021

Published on: 18 July, 2020

Page: [19 - 30] Pages: 12

DOI: 10.2174/1567201817666200719005440

Price: $65

conference banner
Abstract

Aim: This study aimed to explore an affordable technique for the fabrication of Chitosan Nanoshuttles (CSNS) at the ultrafine nanoscale less than 100 nm with improved physicochemical properties, and cytotoxicity on the MCF-7 cell line.

Background: Despite several studies reported that the antitumor effect of CS and CSNS could achieve intracellular compartment target ability, no enough information is available about this issue and further studies are required to address this assumption.

Objectives: The objective of the current study was to investigate the potential processing variables for the production of ultrafine CSNS (less than; 100 nm) using Box-Behnken Design factorial design (BBD). This was achieved through a study of the effects of processing factors, such as CS concentration, CS/TPP ratio, and pH of the CS solution, on PS, PDI, and ZP. Moreover, the obtained CSNS was evaluated for physicochemical characteristics, morphology. In addition, hemocompatibility and cytotoxicity using Red Blood Cells (RBCs) and MCF-7 cell lines were investigated.

Methods: Box-Behnken Design factorial design (BBD) was used in the analysis of different selected variables. The effects of CS concentration, sodium tripolyphosphate (TPP) ratio, and pH on particle size, Polydispersity Index (PDI), and Zeta Potential (ZP) were measured. Subsequently, the prepared CS nanoshuttles were exposed to stability studies, physicochemical characterization, hemocompatibility, and cytotoxicity using red blood cells and MCF-7 cell lines as surrogate models for in vivo study.

Result: The present results revealed that the optimized CSNS has ultrafine nanosize, (78.3 ± 0.22 nm), homogenous with PDI (0.131 ± 0.11), and ZP (31.9 ± 0.25 mV). Moreover, CSNS has a spherical shape, amorphous in structure, and physically stable. Moreover, CSNS has biological safety as indicated by a gentle effect on red blood cell hemolysis, besides, the obtained nanoshuttles decrease MCF-7 viability.

Conclusion: The present findings concluded that the developed ultrafine CSNS has unique properties with enhanced cytotoxicity, thus promising for use in intracellular organelles drug delivery.

Keywords: Chitosan, nanoshuttles, Box-Benhken Design, biocompatibility, cytotoxicity, drug delivery.

Graphical Abstract
[1]
Harisa, G.I.; Faris, T.M. Direct drug targeting into intracellular compartments: Issues, limitations, and future outlook. J. Membr. Biol., 2019, 252(6), 527-539.
[http://dx.doi.org/10.1007/s00232-019-00082-5] [PMID: 31375855]
[2]
Harisa, G.I.; Badran, M.M.; Alanazi, F.K.; Attia, S.M. Crosstalk of nanosystems induced extracellular vesicles as promising tools in biomedical applications. J. Membr. Biol., 2017, 250(6), 605-616.
[http://dx.doi.org/10.1007/s00232-017-0003-x] [PMID: 29127486]
[3]
Harisa, G.I.; Badran, M.M.; Alanazi, F.K.; Attia, S.M. An overview of nanosomes delivery mechanisms: trafficking, orders, barriers and cellular effects. Artif. Cells Nanomed. Biotechnol., 2018, 46(4), 669-679.
[http://dx.doi.org/10.1080/21691401.2017.1354301] [PMID: 28701048]
[4]
Buzea, C.; Pacheco, I.I.; Robbie, K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases, 2007, 2(4), MR17-MR71.
[http://dx.doi.org/10.1116/1.2815690] [PMID: 20419892]
[5]
Shariatinia, Z. Pharmaceutical applications of chitosan. Adv. Colloid Interface Sci., 2019, 263, 131-194.
[http://dx.doi.org/10.1016/j.cis.2018.11.008] [PMID: 30530176]
[6]
Harisa, G.I.; Attia, S.M.; Zoheir, K.M.A.; Alanazi, F.K. Chitosan treatment abrogates hypercholesterolemia-induced erythrocyte’s arginase activation. Saudi Pharm. J., 2017, 25(1), 120-127.
[http://dx.doi.org/10.1016/j.jsps.2016.05.007] [PMID: 28223872]
[7]
Selvasudha, N.; Koumaravelou, K. The multifunctional synergistic effect of chitosan on simvastatin loaded nanoparticulate drug delivery system. Carbohydr. Polym., 2017, 163, 70-80.
[http://dx.doi.org/10.1016/j.carbpol.2017.01.038] [PMID: 28267520]
[8]
Bugnicourt, L.; Ladavière, C. Interests of chitosan nanoparticles ionically cross-linked with tripolyphosphate for biomedical applications. Prog. Polym. Sci., 2016, 60, 1-17.
[http://dx.doi.org/10.1016/j.progpolymsci.2016.06.002]
[9]
Naskar, S.; Koutsu, K.; Sharma, S. Chitosan-based nanoparticles as drug delivery systems: a review on two decades of research. J. Drug Target., 2019, 27(4), 379-393.
[http://dx.doi.org/10.1080/1061186X.2018.1512112] [PMID: 30103626]
[10]
Kumar, B.; Jalodia, K.; Kumar, P.; Gautam, H.K. Recent advances in nanoparticle-mediated drug delivery. J. Drug Deliv. Sci. Technol., 2017, 41, 260-268.
[http://dx.doi.org/10.1016/j.jddst.2017.07.019]
[11]
Mohammed, M.A.; Syeda, J.T.M.; Wasan, K.M.; Wasan, E.K. An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics, 2017, 9(4), 1-26.
[http://dx.doi.org/10.3390/pharmaceutics9040053] [PMID: 29156634]
[12]
Antoniou, J.; Liu, F.; Majeed, H.; Qi, J.; Yokoyama, W.; Zhong, F. Physicochemical and morphological properties of size-controlled chitosan-tripolyphosphate nanoparticles. Colloids Surf. A Physicochem. Eng. Asp., 2015, 465, 137-146.
[http://dx.doi.org/10.1016/j.colsurfa.2014.10.040]
[13]
Calvo, P.; Remuñán-López, C.; Vila-Jato, J.L.; Alonso, M.J. Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. J. Appl. Polym. Sci., 1997, 63(1), 125-132.
[http://dx.doi.org/10.1002/(SICI)1097-4628(19970103)63:1<125:AID-APP13>3.0.CO;2-4]
[14]
Fan, W.; Yan, W.; Xu, Z.; Ni, H. Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids Surf. B Biointerfaces, 2012, 90, 21-27.
[http://dx.doi.org/10.1016/j.colsurfb.2011.09.042] [PMID: 22014934]
[15]
Abdel-Hafez, S.M.; Hathout, R.M.; Sammour, O.A. Towards better modeling of chitosan nanoparticles production: screening different factors and comparing two experimental designs. Int. J. Biol. Macromol., 2014, 64, 334-340.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.11.041] [PMID: 24355618]
[16]
de Pinho Neves, A.L.; Milioli, C.C.; Müller, L.; Riella, H.G.; Kuhnen, N.C.; Stulzer, H.K. Factorial design as tool in chitosan nanoparticles development by ionic gelation technique. Colloids Surf. A Physicochem. Eng. Asp., 2014, 445, 34-39.
[http://dx.doi.org/10.1016/j.colsurfa.2013.12.058]
[17]
Thandapani, G.; P, S.P.; P N, S.; Sukumaran, A. Size optimization and in vitro biocompatibility studies of chitosan nanoparticles. Int. J. Biol. Macromol., 2017, 104(Pt B), 1794-1806.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.08.057] [PMID: 28807691]
[18]
Huang, Y.; Cai, Y.; Lapitsky, Y. Factors affecting the stability of chitosan/tripolyphosphate micro- and nanogels: resolving the opposing findings. J. Mater. Chem. B, 2015, 3(29), 5957-5970.
[19]
Gong, X.; Wang, Y.; Kuang, T. ZIF-8-based membranes for carbon dioxide capture and separation. ACS Sustain. Chem.& Eng., 2017, 5(12), 11204-11214.
[20]
Ma, W.; Li, W.; Liu, R.; Cao, M.; Zhao, X.; Gong, X. Carbon dots and AIE molecules for highly efficient tandem luminescent solar concentrators. Chem. Commun. (Camb.), 2019, 55(52), 7486-7489.
[http://dx.doi.org/10.1039/C9CC02676B] [PMID: 31184645]
[21]
Li, Z.; Zhao, X.; Huang, C.; Gong, X. Recent advances in green fabrication of luminescent solar concentrators using nontoxic quantum dots as fluorophores. J. Mater. Chem. C Mater. Opt. Electron. Devices, 2019, 7(40), 12373-12387.
[http://dx.doi.org/10.1039/C9TC03520F]
[22]
Wang, Y.; Gong, X. Superhydrophobic coatings with periodic ring structured patterns for self-cleaning and oil-water separation. Adv. Mater. Interfaces, 2017, 4(16), 1700-1190.
[http://dx.doi.org/10.1002/admi.201700190]
[23]
Zhong, L.; Gong, X. Phase separation-induced superhydrophobic polylactic acid films. Soft Matter, 2019, 15(46), 9500-9506.
[http://dx.doi.org/10.1039/C9SM01624D] [PMID: 31702749]
[24]
Peng, J.; Zhao, X.; Wang, W.; Gong, X. Durable self-cleaning surfaces with superhydrophobic and highly oleophobic properties. Langmuir, 2019, 35(25), 8404-8412.
[http://dx.doi.org/10.1021/acs.langmuir.9b01507] [PMID: 31192609]
[25]
Han, J.; Yue, Y.; Wu, Q.; Huang, C.; Pan, H.; Zhan, X. Effects of nanocellulose on the structure and properties of poly(vinyl alcohol)-borax hybrid foams. Cellulose, 2017, 24(10), 4433-4448.
[http://dx.doi.org/10.1007/s10570-017-1409-4]
[26]
Liang, J.; Huang, C.; Gong, X. Silicon nanocrystals and their composites: syntheses, fluorescence mechanisms, and biological applications. ACS Sustain. Chem.& Eng., 2019, 7(22), 18213-18227.
[http://dx.doi.org/10.1021/acssuschemeng.9b04359]
[27]
Alatorre-Meda, M.; Taboada, P.; Sabín, J.; Krajewska, B.; Varela, L.M.; Rodríguez, J.R. DNA-chitosan complexation: a dynamic light scattering study. Colloids Surf. A Physicochem. Eng. Asp., 2009, 339(1), 145-152.
[http://dx.doi.org/10.1016/j.colsurfa.2009.02.014]
[28]
Yen, M.T.; Yang, J.H.; Mau, J.L. Physicochemical characterization of chitin and chitosan from crab shells. Carbohydr. Polym., 2009, 75(1), 15-21.
[http://dx.doi.org/10.1016/j.carbpol.2008.06.006]
[29]
Zhou, Y.; Li, J.; Lu, F.; Deng, J.; Zhang, J.; Fang, P.; Peng, X.; Zhou, S.F. A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells. Drug Des. Devel. Ther., 2015, 9, 2635-2645.
[PMID: 25999697]
[30]
Shah, B.; Khunt, D.; Misra, M.; Padh, H. Application of Box-Behnken design for optimization and development of quetiapine fumarate loaded chitosan nanoparticles for brain delivery via intranasal route*. Int. J. Biol. Macromol., 2016, 89, 206-218.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.04.076] [PMID: 27130654]
[31]
Pan, C.; Qian, J.; Fan, J.; Guo, H.; Gou, L.; Yang, H. Preparation nanoparticle by ionic cross-linked emulsified chitosan and its antibacterial activity. Colloids Surf. A Physicochem. Eng. Asp., 2019, 568, 362-370.
[http://dx.doi.org/10.1016/j.colsurfa.2019.02.039]
[32]
Alomrani, A.; Badran, M.; Harisa, G.I. ALshehry, M.; Alhariri, M.; Alshamsan, A.; Alkholief, M. The use of chitosan-coated flexible liposomes as a remarkable carrier to enhance the antitumor efficacy of 5-fluorouracil against colorectal cancer. Saudi Pharm. J., 2019, 27(5), 603-611.
[http://dx.doi.org/10.1016/j.jsps.2019.02.008] [PMID: 31297013]
[33]
Alshraim, M.O.; Sangi, S.; Harisa, G.I.; Alomrani, A.H.; Yusuf, O.; Badran, M.M. Chitosan-coated flexible liposomes magnify the anticancer activity and bioavailability of docetaxel: impact on composition. Molecules, 2019, 24(2), 250.
[http://dx.doi.org/10.3390/molecules24020250] [PMID: 30641899]
[34]
Loh, J.W.; Yeoh, G.; Saunders, M.; Lim, L.Y. Uptake and cytotoxicity of chitosan nanoparticles in human liver cells. Toxicol. Appl. Pharmacol., 2010, 249(2), 148-157.
[http://dx.doi.org/10.1016/j.taap.2010.08.029] [PMID: 20831879]
[35]
Loh, J.W.; Saunders, M.; Lim, L-Y. Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells. Toxicol. Appl. Pharmacol., 2012, 262(3), 273-282.
[http://dx.doi.org/10.1016/j.taap.2012.04.037] [PMID: 22609640]
[36]
Mazzotta, E.; De Benedittis, S.; Qualtieri, A.; Muzzalupo, R. Actively targeted and redox responsive delivery of anticancer drug by chitosan nanoparticles. Pharmaceutics, 2019, 26(1), 12.
[http://dx.doi.org/10.3390/pharmaceutics12010026]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy