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.

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Published

02.12.2023 — Updated on 12.04.2024

Issue

Vol. 30 No. 3 (2024)

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

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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

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