FUNCTIONALIZED CARBON NANOSTRUCTURES AS TEMOZOLOMIDE CARRIERS: PHYSICOCHEMICAL AND BIOPHARMACEUTICAL CHARACTERIZATION Original scientific paper
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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.
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International Atomic Energy Agency
Grant numbers MAK1003
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.