FUNCTIONALIZED CARBON NANOSTRUCTURES AS TEMOZOLOMIDE CARRIERS: PHYSICOCHEMICAL AND BIOPHARMACEUTICAL CHARACTERIZATION

Original scientific paper

Authors

  • Radmila Milenkovska Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Blv. Mother Theresa No. 45, 1000 Skopje, Republic of N Macedonia https://orcid.org/0009-0004-8227-4298
  • Nikola Geskovski Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Str. Arhimedova No. 5, 1000 Skopje, Republic of N Macedonia https://orcid.org/0000-0002-2073-5632
  • Petre Makreski Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Str. Arhimedova No. 5, 1000 Skopje, Republic of N Macedonia https://orcid.org/0000-0003-0662-5995
  • Anita Grozdanov Faculty of Technology and Metallurgy, Ss. Cyril and Methodius University in Skopje, Str. Rugjer Boshkovikj No. 16, 1000 Skopje, Republic of N Macedonia
  • Emil Popovski Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Str. Arhimedova No. 5, 1000 Skopje, Republic of N Macedonia https://orcid.org/0000-0002-6673-0917
  • Gjorgji Petrushevski Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Str. Arhimedova No. 5, 1000 Skopje, Republic of N Macedonia and Alkaloid AD Skopje, Blv. Aleksandar Makedonski No. 12, 1000 Skopje, Republic of N Macedonia
  • Maja Simonoska Crcarevska Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Blv. Mother Theresa No. 45, 1000 Skopje, Republic of N Macedonia https://orcid.org/0000-0002-1927-7101
  • Kristina Mladenovska Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Blv. Mother Theresa No. 45, 1000 Skopje, Republic of N Macedonia https://orcid.org/0000-0003-2503-4699

DOI:

https://doi.org/10.2298/CICEQ230505027M

Keywords:

multiwalled carbon nanotube, graphene, polyethylene glycol, temozolomide, physicohemical properties, sustained release

Abstract

In this study, temozolomide (TMZ), a drug used in the treatment of anaplastic astrocytoma and glioblastoma multiforme, was incorporated in multiwalled carbon nanotubes (MWCNTs) and hybrid carbon nanotubes with graphene (MWCNTs-G) functionalized by polyethylene glycol (PEG). The aim was to evaluate the potential of these nanocarriers for targeted delivery and sustained release of TMZ in brain tumor cells. Oxidized MWCNTs and MWCNTs-G were noncovalently functionalized with PEGs of different molecular weights and subsequently loaded with TMZ following standard procedures. Thorough physicochemical and biopharmaceutical characterization of the TMZ-loaded carbon nanocarriers pointed to high encapsulation efficacy (up to 67%) and drug loading (up to 18% out of 25% theoretical value) and homogeneous particle size distribution, with z-average (160 to 300 nm) and zeta potential (–31 to –21 mV) of the particles adequate for crossing the blood-brain-tumor-barrier (BBTB) and entering into the tumor cells. Successful functionalization and TMZ loading were confirmed by SEM and TEM images, UV-Vis absorption, infrared and Raman spectroscopy, and TGA analyses. Sustained release of TMZ from the carbon nanocarriers was observed in vitro. The presented findings form a fundamental platform for further investigation of these formulations against different types of glioma cells and in adequate animal models.

References

Y. Zhou, K. Vinothini, F. Dou, Y. Jing, A. A. Chuturgoon, T. Arumugam, M. Rajan, Arabian J. Chem. 15 (2022) 103649. https://doi.org/10.1016/j.arabjc.2021.103649.

L. Wu, C. Man, H. Wang, X. Lu, Q. Ma, Y. Cai, W. Ma, Pharm. Res. 30 (2013) 412—423. https://doi.org/10.1007/S11095-012-0883-5

R. Singh, N.K. Mehra, V. Jain, N.K. Jain, J. Drug Targeting 21 (2013) 581—592. https://doi.org/10.3109/1061186X.2013.778264.

B. Zhang, Y. Xing, Z. Li, H. Zhou, Q. Mu, B. Yan, Nano Lett. 9 (2009) 2280—2284. https://doi.org/10.1021/nl900437n.

D. Pantarotto, R. Singh, D. McCarthy, M. Erhardt, J.P. Briand, M. Prato, K. Kostarelos, A. Bianco, Angew. Chem. 43 (2004) 5242—5246. https://doi.org/10.1002/anie.200460437.

A. Masotti, M.R. Miller, A. Celluzzi, L. Rose, F. Micciulla, P.W.F. Hadoke, S. Belluci, A. Caporali, Nanomed. Nanotehnol. Biol. Med. 12 (2016) 1511—1522. https://doi.org/10.1016/j.nano.2016.02.017.

H. Sun, J. Ren, X. Qu, Acc. Chem. Res. 49 (2016) 461—470. https://doi.org/10.1021/acs.accounts.5b00515.

N. Jawahar, A. De, S. Jubee, E.S. Reddy, Drug Dev. Res. 81 (2019) 305—314. https://doi.org/10.1002/ddr.21620.

Y. Wu, J.A. Phillips, H. Liu, R. Yang, W. Tan, ACS Nano 2 (2008) 2023—2028. https://doi.org/10.1021/NN800325A.

P. Wolski, K. Nieszporek, T. Panczyk, Phys. Chem. Chem. Phys. 19 (2017) 9300—9312. https://doi.org/10.1039/C7CP00702G.

B.S. Wong, S.L. Yoong, A. Jagusiak, T. Panczyk, H.K. Ho, W.H. Ang, G. Pastorin, Adv. Drug Delivery Rev. 65 (2013) 1964—2015. https://doi.org/10.1016/j.addr.2013.08.005.

X. Zhao, K. Tian, T. Zhou, X. Jia, J. Li, P. Liu, Colloids Surf. B 168 (2018) 43—49. https://doi.org/10.1016/j.colsurfb.2018.02.041.

D. Ravelli, D. Merli, E. Quartarone, A. Profumo, P. Mustarelli, M. Fagnoni, RSC Adv. 3 (2013) 13569—13582. https://doi.org/10.1039/C3RA40852C.

A. Di Martino, P. Kucharczyk, Z. Capakova, P. Humpolicek, V. Sedlarik, J. Nanopart. Res. 19 (2017) 1—16. https://doi.org/10.1007/s11051-017-3756-3.

J.S. Ananta, R. Paulmurugan, T.F. Massoud, Neurol. Res. 38 (2016) 51—59. https://doi.org/10.1080/01616412.2015.1133025.

A.A. John, A.P. Subramanian, M.V. Vellayappan, A. Balaji, H. Mohandas, S. Jaganathan, Int. J. Nanomed. 10 (2015) 4267—4277. https://doi.org/10.2147/IJN.S83777.

C.Y. Lee, I.H. Ooi, Pharmaceuticals 9 (2016) 54. https://doi.org/10.3390/PH9030054.

Q. Guo, X. Shen, Y. Li, S. Xu, Curr. Med. Sci. 37 (2017) 635—641. https://doi.org/10.1007/s11596-017-1783-z.

H. Huang, Q. Yuan, J.S. Shah, R.D.K. Misra, Adv. Drug Delivery Rev. 63 (2011) 1332—1339. https://doi.org/10.1016/j.addr.2011.04.001.

L. Niu, L. Meng, Q. Lu, Macromol. Biosci. 13 (2013) 735—744. https://doi.org/10.1002/mabi.201200475.

A. Jain, G. Chasoo, S.K. Singh, A.K. Saxena, S.K. Jain, J. Microencapsulation 28 (2011) 21—28. https://doi.org/10.3109/02652048.2010.522257.

X. Wei, X. Chen, M. Ying, W. Lu, Acta Pharm. Sin. B 4 (2014) 193—201.

https://doi.org/10.1016/j.apsb.2014.03.001.

S. Honary, F. Zahir, Trop. J. Pharm. Res. 12 (2013) 255—264. https://doi.org/10.4314/tjpr.v12i2.19.

Y. Yamamoto, Y. Nagasaki, Y. Kato, Y. Sugiyama, K. Kataoka, J. Controlled Release 77 (2001) 27—38. https://doi.org/10.1016/s0168-3659(01)00451-5.

Y.Y. Yuan, C. Mao, X. Du, J. Du, F. Wang, J. Wang, Adv. Mater. 24 (2012) 5476—5480. https://doi.org/10.1002/adma.201202296.

C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, L. Bernardino, J. Controlled Release 235 (2016) 34—47. https://doi.org/10.1016/j.jconrel.2016.05.044.

A. Prokop, J.M. Davidson, J. Pharma. Sci. 97 (2018) 3518—3590. https://doi.org/10.1002/jps.21270.

H. Gao, Acta Pharm. Sin. B 6 (2016) 268—286. https://doi.org/10.1016/j.apsb.2016.05.013.

N. Sciortino, S. Fedeli, P. Paoli, A. Brandi, P. Chiarugi, M. Severi, S. Cicchi, Int. J. Pharm. 521 (2017) 69—72. https://doi.org/10.1016/j.ijpharm.2017.02.023.

X. Cui, B. Wan, Y. Yang, X. Ren, L. Guo, Sci. Rep. 7 (2017) 1—13. https://doi.org/10.1038/s41598-017-01746-9.

J. Ren, S. Shen, D. Wang, Z. Xi, L. Guo, Z. Pang, Y. Qian, X. Sun, X. Jiang, Biomaterials 33 (2012) 3324—3333. https://doi.org/10.1016/j.biomaterials.2012.01.025.

V. Miranda-Goncalves, R.M. Reis, F. Baltazar, Curr. Cancer Drug Targets 16 (2016) 388—399. https://doi.org/10.2174/1568009616666151222150543.

A. Orza, O. Soriţǎu, C. Tomuleasa, L. Olenic, A. Florea, O. Pana, I. Bratu, E. Pall, S. Florian, D. Casciano, A. Biris, T. Yoshiyuki, Int. J. Nanomed. 8 (2013) 689—702. https://doi.org/10.2147/IJN.S37481

L. Wang, Z. Wang, Z. Liang, G. Li, S. Duan, Y. Xi, Am. J. Transl. Res. 14 (2022) 5669—5676. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9452319/pdf/ajtr0014-5669.pdf.

S. Romano-Feinholz, A. Salazar-Ramiro, E.M. Sandoval, R. Magaña-Maldonado, N.H. Pedro, E.R. López, G.A. Aguilar, A.S. Garcia, J. Sotelo, P.V. Cruz, B. Pineda, Int. J. Nanomedicine 12 (2017) 6005—6026. https://doi.org/10.2147/IJN.S139004.

M.Q. Zhao, X.F. Liu, Q. Zhang, G.L. Tian, J.Q. Huang, W. Zhu, F. Wei, ACS Nano 6 (2012) 10759—10769. http://doi.org/10.1021/nn304037d.

N. Hadidi, F. Kobarfard, N. Nafissi-Varcheh, R. Aboofazeli, Int. J. Nanomed. 6 (2011) 737—746. https://doi.org/10.2147/ijn.s17626.

B.V. Farahani, G.R. Behbahani, N. Javadi, J. Braz. Chem. Soc. 27 (2016) 694—705. https://doi.org/10.5935/0103-5053.20150318.

J. Chen, H. Liu, C. Zhao, G. Qin, G. Xi, T. Li, X. Wang, T. Chen, Biomaterials 35 (2014) 4986—4995. https://doi.org/10.1016/j.biomaterials.2014.02.032.

B. Gürten, E. Yenigül, A.D. Sezer, S. Malta, Braz. J. Pharm. Sci. 54 (2018) e17513. http://dx.doi.org/10.1590/s2175-97902018000217513.

Cover

Downloads

Published

02.12.2023 — Updated on 12.04.2024

Issue

Vol. 30 No. 3 (2024)

Section

Articles

License

Copyright (c) 2023 Radmila Milenkovska, Nikola Geskovski, Petre Makreski, Anita Grozdanov, Emil Popovski, Gjorgji Petrushevski, Maja Simonoska Crcarevska, Kristina Mladenovska

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Authors who publish with this journal agree to the following terms:

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

Authors grant to the Publisher the following rights to the manuscript, including any supplemental material, and any parts, extracts or elements thereof:

  • the right to reproduce and distribute the Manuscript in printed form, including print-on-demand;
  • the right to produce prepublications, reprints, and special editions of the Manuscript;
  • the right to translate the Manuscript into other languages;
  • the right to reproduce the Manuscript using photomechanical or similar means including, but not limited to photocopy, and the right to distribute these reproductions;
  • the right to reproduce and distribute the Manuscript electronically or optically on any and all data carriers or storage media – especially in machine readable/digitalized form on data carriers such as hard drive, CD-Rom, DVD, Blu-ray Disc (BD), Mini-Disk, data tape – and the right to reproduce and distribute the Article via these data carriers; 
  • the right to store the Manuscript in databases, including online databases, and the right of transmission of the Manuscript in all technical systems and modes;
  • the right to make the Manuscript available to the public or to closed user groups on individual demand, for use on monitors or other readers (including e-books), and in printable form for the user, either via the internet, other online services, or via internal or external networks.

How to Cite

FUNCTIONALIZED CARBON NANOSTRUCTURES AS TEMOZOLOMIDE CARRIERS: PHYSICOCHEMICAL AND BIOPHARMACEUTICAL CHARACTERIZATION: Original scientific paper. (2024). Chemical Industry & Chemical Engineering Quarterly, 30(3), 243-256. https://doi.org/10.2298/CICEQ230505027M

Funding data

Similar Articles

1-10 of 51

You may also start an advanced similarity search for this article.