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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Research Article

Radiopharmacokinetics of Graphene Quantum Dots Nanoparticles In vivo: Comparing the Pharmacokinetics Parameters in Long and Short Periods

Author(s): Matheus Keuper Bastos, Martha Sahylí Ortega Pijeira, Juliana Helena de Souza Sobrinho, Ana Paula dos Santos Matos, Eduardo Ricci-Junior, Pierre Basilio de Almeida Fechine, Luciana Magalhães Rebelo Alencar, Sara Gemini-Piperni, Frank Alexis, Mohamed Fathy Attia and Ralph Santos-Oliveira*

Volume 22, Issue 30, 2022

Published on: 30 June, 2022

Page: [2527 - 2533] Pages: 7

DOI: 10.2174/1568026622666220512150625

Price: $65

Abstract

Background: Nanoparticles (NPs) have gained great importance during the last decades for developing new therapeutics with improved outcomes for biomedical applications due to their nanoscale size, surface properties, loading capacity, controlled drug release, and distribution. Among the carbon-based nanomaterials, one of the most biocompatible forms of graphene is graphene quantum dots (GQDs). GQDs are obtained by converting 2D graphene into zero-dimensional graphene nanosheets. Moreover, very few reports in the literature reported the pharmacokinetic studies proving the safety and effectiveness of GQDs for in vivo applications.

Objectives: This study evaluated the pharmacokinetics of GQDs radiolabeled with 99mTc, administered intravenously, in rodents (Wistar rats) in two conditions: short and long periods, to compare and understand the biological behavior.

Methods: The graphene quantum dots were produced and characterized by RX diffractometry, Raman spectroscopy, and atomic force microscopy. The pharmacokinetic analysis was performed following the radiopharmacokinetics concepts, using radiolabeled graphene quantum dots with technetium 99 metastable (99mTc). The radiolabeling process of the graphene quantum dots with 99mTc was performed by the direct via.

Results: The results indicate that the pharmacokinetic analyses with GQDs over a longer period were more accurate. Following a bicompartmental model, the long-time analysis considers each pharmacokinetic phase of drugs into the body. Furthermore, the data demonstrated that short-time analysis could lead to distortions in pharmacokinetic parameters, leading to misinterpretations.

Conclusion: The evaluation of the pharmacokinetics of GQDs over long periods is more meaningful than the evaluation over short periods.

Keywords: Graphene quantum dots, Pharmacokinetics, In vivo analyses, 99mTc labeling, Nanoparticles, GQDs.

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[1]
Maiti, D.; Tong, X.; Mou, X.; Yang, K. Carbon-based nanomaterials for biomedical applications: A recent study. Front. Pharmacol., 2019, 9, 1401.
[http://dx.doi.org/10.3389/fphar.2018.01401] [PMID: 30914959]
[2]
Magne, T.M.; de Oliveira Vieira, T.; Alencar, L.M.R.; Junior, F.F.M.; Gemini-Piperni, S.; Carneiro, S.V.; Fechine, L.M.U.D.; Freire, R.M.; Golokhvast, K.; Metrangolo, P.; Fechine, P.B.A.; Santos-Oliveira, R. Graphene and its derivatives: Understanding the main chemical and medicinal chemistry roles for biomedical applications. J. Nanostructure Chem., 2021, 1-35.
[http://dx.doi.org/10.1007/s40097-021-00444-3] [PMID: 34512930]
[3]
Novoselov, K.S.; Fal’ko, V.I.; Colombo, L.; Gellert, P.R.; Schwab, M.G.; Kim, K. A roadmap for graphene. Nature, 2012, 490(7419), 192-200.
[http://dx.doi.org/10.1038/nature11458] [PMID: 23060189]
[4]
Gurunathan, S.; Kim, J.H. Synthesis, toxicity, biocompatibility, and biomedical applications of graphene and graphene-related materials. Int. J. Nanomedicine, 2016, 11, 1927-1945.
[http://dx.doi.org/10.2147/IJN.S105264] [PMID: 27226713]
[5]
Novoselov, K.S.; Geim, A.K.; Morozov, S.V. Electric field effect in atomically thin carbon films. Science, 2004, 306(80), 666-669.
[6]
Haque, E.; Kim, J.; Malgras, V.; Reddy, K.R.; Ward, A.C.; You, J.; Bando, Y.; Hossain, M.S.A.; Yamauchi, Y. Recent advances in graphene quantum dots: Synthesis, properties, and applications. Small Methods, 2018, 2(10), 1-14.
[http://dx.doi.org/10.1002/smtd.201800050]
[7]
Tian, P.; Tang, L.; Teng, K.S.; Lau, S.P. Graphene quantum dots from chemistry to applications. Mater. Today Chem., 2018, 10, 221-258.
[http://dx.doi.org/10.1016/j.mtchem.2018.09.007]
[8]
Henna, T.K.; Pramod, K. Graphene quantum dots redefine nanobiomedicine. Mater. Sci. Eng. C, 2020, 110, 110651.
[http://dx.doi.org/10.1016/j.msec.2020.110651] [PMID: 32204078]
[9]
Zheng, X.T.; Ananthanarayanan, A.; Luo, K.Q.; Chen, P. Glowing graphene quantum dots and carbon dots: Properties, syntheses, and biological applications. Small, 2015, 11(14), 1620-1636.
[http://dx.doi.org/10.1002/smll.201402648] [PMID: 25521301]
[10]
Dos Reis, S.R.R.; Pinto, S.R.; de Menezes, F.D.; Martinez-Manez, R.; Ricci-Junior, E.; Alencar, L.M.R.; Helal-Neto, E.; da Silva de Barros, A.O.; Lisboa, P.C.; Santos-Oliveira, R. Senescence and the impact on biodistribution of different nanosystems: The discrepancy on tissue deposition of graphene quantum dots, polycaprolactone nanoparticle and magnetic mesoporous silica nanoparticles in young and elder animals. Pharm. Res., 2020, 37(3), 40.
[http://dx.doi.org/10.1007/s11095-019-2754-9] [PMID: 31970499]
[11]
Wu, S.; Helal-Neto, E.; Matos, A.P.D.S.; Jafari, A.; Kozempel, J.; Silva, Y.J.A.; Serrano-Larrea, C.; Alves, Junior, S.; Ricci-Junior, E.; Alexis, F.; Santos-Oliveira, R. Radioactive polymeric nanoparticles for biomedical application. Drug Deliv., 2020, 27(1), 1544-1561.
[http://dx.doi.org/10.1080/10717544.2020.1837296] [PMID: 33118416]
[12]
Zhao, C.; Song, X.; Liu, Y. Synthesis of graphene quantum dots and their applications in drug delivery. J. Nanobiotechnology, 2020, 18, 142.
[http://dx.doi.org/10.1186/s12951-020-00698-z]
[13]
Lu, H.; Li, W.; Dong, H.; Wei, M. Graphene quantum dots for optical bioimaging. Small, 2019, 15(36), e1902136.
[http://dx.doi.org/10.1002/smll.201902136] [PMID: 31304647]
[14]
Mansuriya, B.D.; Altintas, Z. Applications of graphene quantum dots in biomedical sensors. Sensors (Basel), 2020, 20(4), 1-71.
[http://dx.doi.org/10.3390/s20041072] [PMID: 32079119]
[15]
Li, R.E.; Li, Y.R.; Zhu, H.; Jia, Z. Graphene quantum dots potently block copper-mediated oxidative DNA damage: Implications for cancer intervention. React. Oxyg. Species (Apex), 2018, 6(18), 406-413.
[PMID: 30465025]
[16]
Ruan, J.; Wang, Y.; Li, F.; Jia, R.; Zhou, G.; Shao, C.; Zhu, L.; Cui, M.; Yang, D.P.; Ge, S. Graphene quantum dots for radiotherapy. ACS Appl. Mater. Interfaces, 2018, 10(17), 14342-14355.
[http://dx.doi.org/10.1021/acsami.7b18975] [PMID: 29542912]
[17]
Rai, A.; Noor, S.; Ahmad, S.I.; Alajmi, M.F.; Hussain, A.; Abbas, H.; Hasan, G.M. Recent advances and implication of bioengineered nanomaterials in cancer theranostics. Medicina (Kaunas), 2021, 57(2), 1-25.
[http://dx.doi.org/10.3390/medicina57020091] [PMID: 33494239]
[18]
Perini, G.; Palmieri, V.; Ciasca, G.; De Spirito, M.; Papi, M. Unravelling the potential of graphene quantum dots in biomedicine and neuroscience. Int. J. Mol. Sci., 2020, 21(10), 1-25.
[http://dx.doi.org/10.3390/ijms21103712] [PMID: 32466154]
[19]
Tak, K.; Sharma, R.; Dave, V.; Jain, S.; Sharma, S. Clitoria ternatea mediated synthesis of graphene quantum dots for the treatment of Alzheimer’s Disease. ACS Chem. Neurosci., 2020, 11(22), 3741-3748.
[http://dx.doi.org/10.1021/acschemneuro.0c00273] [PMID: 33119989]
[20]
Wei, K.; Liu, F.; Yang, J.; Huo, D.; Guan, G.; Li, Y.; Yang, G.; Wang, T.; Wang, Y.; Nie, Z.; Zeng, W.; Zhu, C. Engineered-macrophage induced endothelialization and neutralization via graphene quantum dot-mediated MicroRNA delivery to construct small-diameter tissue-engineered vascular grafts. J. Biomed. Nanotechnol., 2019, 15(7), 1492-1505.
[http://dx.doi.org/10.1166/jbn.2019.2787] [PMID: 31196353]
[21]
Iannazzo, D.; Pistone, A.; Ferro, S.; De Luca, L.; Monforte, A.M.; Romeo, R.; Buemi, M.R.; Pannecouque, C. Graphene quantum dots based systems as HIV inhibitors. Bioconjug. Chem., 2018, 29(9), 3084-3093.
[http://dx.doi.org/10.1021/acs.bioconjchem.8b00448] [PMID: 30106563]
[22]
Abdifetah, O.; Na-Bangchang, K. Pharmacokinetic studies of nanoparticles as a delivery system for conventional drugs and herb-derived compounds for cancer therapy: A systematic review. Int. J. Nanomedicine, 2019, 14, 5659-5677.
[http://dx.doi.org/10.2147/IJN.S213229] [PMID: 31632004]
[23]
Sinha, R.; Purkayastha, P. Daunomycin delivery by ultrasmall graphene quantum dots to DNA duplexes: Understanding the dynamics by resonance energy transfer. J. Mater. Chem. B Mater. Biol. Med., 2020, 8(42), 9756-9763.
[http://dx.doi.org/10.1039/D0TB01831G] [PMID: 33021304]
[24]
Sung, S.Y.; Su, Y.L.; Cheng, W.; Hu, P.F.; Chiang, C.S.; Chen, W.T.; Hu, S.H. Graphene quantum dots-mediated theranostic penetrative delivery of drug and photolytics in deep tumors by targeted biomimetic nanosponges. Nano Lett., 2019, 19(1), 69-81.
[http://dx.doi.org/10.1021/acs.nanolett.8b03249] [PMID: 30521346]
[25]
Mathew, T.; Sree, R.A.; Aishwarya, S.; Kounaina, K.; Patil, A.G.; Satapathy, P.; Hudeda, S.P.; More, S.S.; Muthucheliyan, K.; Kumar, T.N.; Raghu, A.V.; Reddy, K.R.; Zameer, F. Graphene-based functional nanomaterials for biomedical and bioanalysis applications. FlatChem, 2020, 23, 100184.
[http://dx.doi.org/10.1016/j.flatc.2020.100184]
[26]
Kim, D.; Shin, K.; Kwon, S.G.; Hyeon, T. Synthesis and biomedical applications of multifunctional nanoparticles. Adv. Mater., 2018, 30(49), e1802309.
[http://dx.doi.org/10.1002/adma.201802309] [PMID: 30133009]
[27]
Osman, W.; Abdelsalam, H.; Ali, M.; Teleb, N.H.; Yahia, I.S.; Ibrahim, M.A.; Zhang, Q. Electronic and magnetic properties of graphene quantum dots doped with alkali metals. J. Mater. Res. Technol., 2021, 11, 1517-1533.
[http://dx.doi.org/10.1016/j.jmrt.2021.01.119]
[28]
Siafaka, P.I.; Okur, N.Ü.; Karantas, I.D.; Okur, M.E. Gündoğdu, E.A. Current update on nanoplatforms as therapeutic and diagnostic tools: A review for the materials used as nanotheranostics and imaging modalities. Asian J. Pharmaceut. Sci., 2021, 16(1), 24-46.
[http://dx.doi.org/10.1016/j.ajps.2020.03.003] [PMID: 33613728]
[29]
de Menezes, F.D.; Dos Reis, S.R.R.; Pinto, S.R.; Portilho, F.L.; do Vale Chaves, E. Mello, F.; Helal-Neto, E.; da Silva de Barros, A.O.; Alencar, L.M.R.; de Menezes, A.S.; Dos Santos, C.C.; Saraiva-Souza, A.; Perini, J.A.; Machado, D.E.; Felzenswalb, I.; Araujo-Lima, C.F.; Sukhanova, A.; Nabiev, I.; Santos-Oliveira, R. Graphene quantum dots unraveling: Green synthesis, characterization, radiolabeling with 99mTc, in vivo behavior and mutagenicity. Mater. Sci. Eng. C, 2019, 102, 405-414.
[http://dx.doi.org/10.1016/j.msec.2019.04.058] [PMID: 31147011]
[30]
Amudhalapalli, G.K.; Devanuri, J.K. Synthesis, characterization, thermophysical properties, stability and applications of nanoparticle enhanced phase change materials - A comprehensive review. Therm. Sci. Eng. Prog., 2022, 28, 101049.
[http://dx.doi.org/10.1016/j.tsep.2021.101049]
[31]
Shargel, L.; Yu, A.B.C. Applied Biopharmaceutics & Pharmacokinetics, 7th ed; McGraw-Hill Education: New York, 2016.
[32]
Faqi, A.S. A Comprehensive Guide to Toxicology in Nonclinical Drug Development; Springer: New York, 2017.
[http://dx.doi.org/10.1016/C2015-0-00147-2]
[33]
McLeod, H.L. Pharmacokinetics for the prescriber. Medicine (Abingdon), 2008, 36(7), 350-354.
[http://dx.doi.org/10.1016/j.mpmed.2008.04.003]
[34]
Mansoor, A.; Mahabadi, N. Volume of Distribution; StatPearls Publishing: Treasure Island, 2021.
[35]
Davis, P.J.; Cladis, F.P. Smith’s Anesthesia for Infants and Children Purchase Options; Elsevier: Amsterdam, 2016.
[36]
Franken, L.G.; de Winter, B.C.M.; van Esch, H.J.; van Zuylen, L.; Baar, F.P.; Tibboel, D.; Mathôt, R.A.; van Gelder, T.; Koch, B.C. Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol. Expert Opin. Drug Metab. Toxicol., 2016, 12(6), 669-680.
[http://dx.doi.org/10.1080/17425255.2016.1179281] [PMID: 27081769]
[37]
Deka, M.J.; Dutta, A.; Chowdhury, D. Tuning the wettability and photoluminescence of graphene quantum dots via covalent modification. New J. Chem., 2018, 42(1), 355-362.
[http://dx.doi.org/10.1039/C7NJ03280C]
[38]
Padmanabhan, S. Handbook of Pharmacogenomics and Stratified; Elsevier, 2014, pp. 1-1093.
[39]
Di, L.; Kerns, E. Chapter 19 -Pharmacokinetics. In: Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization; Academic Press: Cambridge, 2016; pp. 267-281.
[http://dx.doi.org/10.1016/B978-0-12-801076-1.00019-8]
[40]
Atlee, J.L. Complications in Anesthesia; Elsevier: Amsterdam, 2007.
[41]
Kadam, R.S.; Bourne, D.W.A.; Kompella, U.B. Nano-advantage in enhanced drug delivery with biodegradable nanoparticles: Contribution of reduced clearance. Drug Metab. Dispos., 2012, 40(7), 1380-1388.
[http://dx.doi.org/10.1124/dmd.112.044925] [PMID: 22498894]
[42]
Licciardello, N.; Hunoldt, S.; Bergmann, R.; Singh, G.; Mamat, C.; Faramus, A.; Ddungu, J.L.Z.; Silvestrini, S.; Maggini, M.; De Cola, L.; Stephan, H. Biodistribution studies of ultrasmall silicon nanoparticles and carbon dots in experimental rats and tumor mice. Nanoscale, 2018, 10(21), 9880-9891.
[http://dx.doi.org/10.1039/C8NR01063C] [PMID: 29658023]
[43]
Tenzer, S.; Docter, D.; Kuharev, J.; Musyanovych, A.; Fetz, V.; Hecht, R.; Schlenk, F.; Fischer, D.; Kiouptsi, K.; Reinhardt, C.; Landfester, K.; Schild, H.; Maskos, M.; Knauer, S.K.; Stauber, R.H. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat. Nanotechnol., 2013, 8(10), 772-781.
[http://dx.doi.org/10.1038/nnano.2013.181] [PMID: 24056901]
[44]
Peng, Q.; Zhang, S.; Yang, Q.; Zhang, T.; Wei, X.Q.; Jiang, L.; Zhang, C.L.; Chen, Q.M.; Zhang, Z.R.; Lin, Y.F. Preformed albumin corona, a protective coating for nanoparticles based drug delivery system. Biomaterials, 2013, 34(33), 8521-8530.
[http://dx.doi.org/10.1016/j.biomaterials.2013.07.102] [PMID: 23932500]
[45]
Milani, S.; Bombelli, F.B.; Pitek, A.S.; Dawson, K.A.; Rädler, J. Reversible versus irreversible binding of transferrin to polystyrene nanoparticles: Soft and hard corona. ACS Nano, 2012, 6(3), 2532-2541.
[http://dx.doi.org/10.1021/nn204951s] [PMID: 22356488]
[46]
Moghimi, S.M.; Hunter, A.C.; Andresen, T.L. Factors controlling nanoparticle pharmacokinetics: An integrated analysis and perspective. Annu. Rev. Pharmacol. Toxicol., 2012, 52(1), 481-503.
[http://dx.doi.org/10.1146/annurev-pharmtox-010611-134623] [PMID: 22035254]
[47]
Pareek, V.; Bhargava, A.; Bhanot, V.; Gupta, R.; Jain, N.; Panwar, J. Formation and characterization of protein corona around nanoparticles: A review. J. Nanosci. Nanotechnol., 2018, 18(10), 6653-6670.
[http://dx.doi.org/10.1166/jnn.2018.15766] [PMID: 29954482]
[48]
Mohammed, B.S.; Cameron, G. The effect of sparse sampling on the prediction error in pharmacokinetics of intravenous paracetamol in children. World J. Pharm. Pharm. Sci., 2019, 8, 1147-1161.
[49]
Loo, T.L.; Tanner, B.B.; Housholder, G.E.; Shepard, B.J. Some pharmacokinetic aspects of 5-(dimethylriazeno)-imidazole-4-carboxamide in the dog. J. Pharm. Sci., 1968, 57(12), 2126-2131.
[http://dx.doi.org/10.1002/jps.2600571221] [PMID: 5715514]
[50]
Scutt, G.; Allen, M.; Waxman, D. Estimating a drug’s elimination rate-constant or half-life from a single blood sample: A practical approach with particular benefits for critically ill/vulnerable patients. Biosystems, 2019, 184, 1-9.
[51]
Colucci, P.; Turgeon, J.; Ducharme, M.P. How critical is the duration of the sampling scheme for the determination of half-life, characterization of exposure and assessment of bioequivalence? J. Pharm. Pharm. Sci., 2011, 14(2), 217-226.
[http://dx.doi.org/10.18433/J3FG63] [PMID: 21733410]
[52]
Bardal, S.K.; Waechter, J.E.; Martin, D.S. Applied Pharmacology; Elsevier: Amsterdam , 2011.
[http://dx.doi.org/10.1097/00003465-199111000-00004]
[53]
Spruill, W.J.; Wade, W.E.; DiPiro, J.T. Concepts in Clinical Pharmacokinetics; Elsevier: Amsterdam 2014.

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