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Metronomic chemotherapy of carboplatin-loaded PEGylated MWCNTs: synthesis, characterization and in vitro toxicity in human breast cancer

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Abstract

Our objective of this study is to design and develop a polyethylene glycol (PEG2000)-modified multiwall carbon nanotube (PEGylated MWCNT) formulation for oral controlled metronomic chemotherapeutic drug delivery. Multiwall carbon nanotubes undergo various chemical modifications including oxidation with strong acids, conjugation of polyethylene glycol, and coating with cellulose acetate phthalate which resulted in the formation of aqueous dispersion and prevention of drug degradation in acidic environment. Advanced analytical procedure such as Fourier transform infra-red, X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, transmission electron microscopy, and dynamic light scattering techniques were used to evaluate physicochemical characterization. We also performed in vitro cytotoxic study by MTT assay and results revealed that carboplatin-loaded PEGylated MWCNTs did not show significant detrimental effect on the viability of MDA-MB-231 (human breast cancer) cells. The maximum encapsulation and drug-loading capacity were determined to be 71.58 ± 0.04 and 39.62 ± 0.07%, respectively. The release of carboplatin from PEGylated MWCNTs was investigated at simulated intestinal fluid (SIF), pH 6.8, after optimizing at simulated gastric fluid (SGF), pH 1.2, by enteric coating. Enteric-coated PEGylated MWCNTs exhibit pH-responsive drug activity in a sustained manner especially at pH 6.8. This surface modification strongly suggests that PEGylated MWCNTs could be a potential carrier for metronomic chemotherapeutic agent for high drug resistance, drug with maximum adverse effect and poorly oral bioavailable drugs.

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References

  1. Ijima S (1991) Helical microtubules of graphitic carbon. Nature 354:56–58

    Article  Google Scholar 

  2. Kayat J, Mehra NK, Gajbhiye V, Jain NK (2015) Drug targeting to arthritic region via folic acid appended surface-engineered multi-walled carbon nanotubes. J Drug Target 24:1–10. https://doi.org/10.3109/1061186x.2015.1077846

    Article  Google Scholar 

  3. Tamer SI, Unsal H, Demiroz FT, Kalaycioglu GD, Degim IT, Aydogan N (2016) Stimuli-responsive lipid nanotubes in gel formulations for the delivery of doxorubicin. Colloids Surf B Biointerfaces 143:406–414

    Article  Google Scholar 

  4. Manasrah AD (2016) Heat transfer enhancement of nanofluids using iron nanoparticles decorated carbon nanotubes. Appl Therm Eng 107:1008–1018

    Article  CAS  Google Scholar 

  5. Etersen ELJP, Enry THBH (2012) Nanomaterials in the environment methodological considerations for testing the ecotoxicity of carbon nanotubes and fullerenes. Environ Toxicol Chem 31:60–72. https://doi.org/10.1002/etc.710

    Article  CAS  Google Scholar 

  6. Saifuddin N, Raziah AZ, Junizah AR (2013) Carbon nanotubes: a review on structure and their interaction with proteins. J Chem. https://doi.org/10.1155/2013/676815

    Article  Google Scholar 

  7. Roy N, Sengupta R, Bhowmick AK (2012) Progress in polymer science modifications of carbon for polymer composites and nanocomposites. Prog Polym Sci 37:781–819. https://doi.org/10.1016/j.progpolymsci.2012.02.002

    Article  CAS  Google Scholar 

  8. Milosavljevic V, Krejcova L, Guran R, Buchtelova H, Wawrzak D, Richtera L, Heger Z, Kopel P, Adam V (2017) Exceptional release kinetics and cytotoxic selectivity of oxidised MWCNTs double-functionalised with doxorubicin and prostate-homing peptide. Colloids Surf B Biointerfaces 156:123–132. https://doi.org/10.1016/j.colsurfb.2017.05.008

    Article  CAS  Google Scholar 

  9. Firme CP, Bandaru PR (2010) Toxicity issues in the application of carbon nanotubes to biological systems. Nanomed Nanotechnol Biol Med 6:245–256. https://doi.org/10.1016/j.nano.2009.07.003

    Article  CAS  Google Scholar 

  10. Marchi LD, Neto V, Pretti C, Figueira E, Chiellini F, Morelli A, Soares AMVM, Freitas R (2018) Toxic effects of multi-walled carbon nanotubes on bivalves: comparison between functionalized and non-functionalized nanoparticles. Sci Total Environ 622:1532–1542. https://doi.org/10.1016/j.scitotenv.2017.10.031

    Article  CAS  Google Scholar 

  11. Kharissova OV, Kharisov BI, Gerardo E, Ortiz EDC (2013) Dispersion of carbon nanotubes in water and non-aqueous solvents. RSC Adv 3:24812–24852. https://doi.org/10.1039/c3ra43852j

    Article  CAS  Google Scholar 

  12. Wu H, Shi H, Zhang H, Wang X, Yang Y, Yu C, Hao C, Du J, Hu H, Yang S (2014) Biomaterials prostate stem cell antigen antibody-conjugated multiwalled carbon nanotubes for targeted ultrasound imaging and drug delivery. Biomaterials 35:5369–5380. https://doi.org/10.1016/j.biomaterials.2014.03.038

    Article  CAS  Google Scholar 

  13. Press D (2011) Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells. Int J Nanomed 6:2889–2898. https://doi.org/10.2147/IJN.S25162

    Article  CAS  Google Scholar 

  14. Zhao Z, Yang Z, Hu Y, Li J, Fan X (2013) Multiple functionalization of multi-walled carbon nanotubes with carboxyl and amino groups. Appl Surf Sci 276:476–481. https://doi.org/10.1016/j.apsusc.2013.03.119

    Article  CAS  Google Scholar 

  15. Dong C, Campell AS, Eldawud R, Perhinschi G, Rojanasakul Y, Zoica C (2013) Effects of acid treatment on structure, properties and biocompatibility of carbon nanotubes. Appl Surf Sci 264:261–268. https://doi.org/10.1016/j.apsusc.2012.09.180

    Article  CAS  Google Scholar 

  16. Wong BS, Yoong SL, Jagusiak A, Panczyk T, Ho HK, Ang WH, Pastorin G (2013) Carbon nanotubes for delivery of small molecule drugs. Adv Drug Deliv Rev 65:1964–2015. https://doi.org/10.1016/j.addr.2013.08.005

    Article  CAS  Google Scholar 

  17. Wen Y, Wu H, Chen S, Lu Y, Shen H, Jia N (2009) Direct electrochemistry and electrocatalysis of hemoglobin immobilized in poly(ethylene glycol) grafted multi-walled carbon nanotubes. Electrochim Acta 54:7078–7084. https://doi.org/10.1016/j.electacta.2009.07.038

    Article  CAS  Google Scholar 

  18. Liu J, Bibari O, Mailley P, Dijon J, Rouvière E, Starace FS, Caillat P, Vineta F, Marchanda G (2009) Stable non-covalent functionalization of multi-walled carbon nanotubes by pyrene–polyethylene glycol through p–p stacking. New J Chem 33:1017–1024. https://doi.org/10.1039/b813085j

    Article  CAS  Google Scholar 

  19. Moore TL, Pitzer JE, Podila R, Wang X, Lewis RL, Grimes SW, Wilson JR, Skjervold E, Brown JM, Rao A, Alexis F (2013) Multifunctional polymer-coated carbon nanotubes for safe drug delivery. Part Part Syst 30:365–373. https://doi.org/10.1002/ppsc.201200145

    Article  CAS  Google Scholar 

  20. Sharma S, Sarkar G, Srestha B, Chattopadhyay D, Bhowmik M (2019) In-situ fast gelling formulation for oral sustained drug delivery of paracetamol to dysphagic patients. Int J Biol Macromol 134:864–868. https://doi.org/10.1016/j.ijbiomac.2019.05.092

    Article  CAS  Google Scholar 

  21. Matter PH, Ozkan US (2006) Non-metal catalysts for dioxygen reduction in an acidic electrolyte. Catal Lett 109:115–123. https://doi.org/10.1007/s10562-006-0067-1

    Article  CAS  Google Scholar 

  22. Rosca ID, Watari F, Uo M, Akasaka T (2005) Oxidation of multiwalled carbon nanotubes by nitric acid. Carbon 43:3124–3131. https://doi.org/10.1016/j.carbon.2005.06.019

    Article  CAS  Google Scholar 

  23. Theiner S, Varbanov HP, Galanski M, Egger AE, Berger W, Heffeter P, Keppler BK (2015) Comparative in vitro and in vivo pharmacological investigation of platinum(IV) complexes as novel anticancer drug candidates for oral application. J Biol Inorg Chem 20:89–99. https://doi.org/10.1007/s00775-014-1214-6

    Article  CAS  Google Scholar 

  24. Sharma S, Naskar S, Kuotsu K (2019) A review on carbon nanotubes: influencing toxicity and emerging carrier for platinum based cytotoxic drug application. J Drug Deliv Sci Technol 51:708–720. https://doi.org/10.1016/j.jddst.2019.02.028

    Article  CAS  Google Scholar 

  25. Wang D, Lippard SJ (2005) Cellular processing of platinum anticancer drugs. Nature 4:307–320. https://doi.org/10.1038/nrd1691

    Article  CAS  Google Scholar 

  26. Cheng Q, Huang HSH, Cao Z, Wang J, Liu Y (2012) Oral delivery of platinum anticancer drug using lipid assisted polymeric nanoparticles. R Soc Chem 51:1–3. https://doi.org/10.1039/x0xx00000x

    Article  Google Scholar 

  27. Lila ASA, Ishida T (2017) Metronomic chemotherapy and nanocarrier platforms. Cancer Lett 400:232–242. https://doi.org/10.1016/j.canlet.2016.11.007

    Article  CAS  Google Scholar 

  28. Kerbel RS, Kamen BA (2004) The anti-angiogenic basis of metronomic chemotherapy. Nature 4:423–436. https://doi.org/10.1038/nrc1369

    Article  CAS  Google Scholar 

  29. Loven D, Hasnis E, Bertolini F, Shaked Y (2018) Low-dose metronomic chemotherapy: from past experience to new paradigms in the treatment of cancer. Drug Discov Today 18:193–201. https://doi.org/10.1016/j.drudis.2012.07.015

    Article  CAS  Google Scholar 

  30. Zhang Z, Feng S (2006) Nanoparticles of poly(lactide)/vitamin E TPGS copolymer for cancer chemotherapy: synthesis, formulation, characterization and in vitro drug release. Biomaterials 27:262–270. https://doi.org/10.1016/j.biomaterials.2005.05.104

    Article  CAS  Google Scholar 

  31. Thanki K, Gangwal RP, Sangamwar AT, Jain S (2013) Oral delivery of anticancer drugs: challenges and opportunities. J Control Release 170:15–40. https://doi.org/10.1016/j.jconrel.2013.04.020

    Article  CAS  Google Scholar 

  32. Singh DH, Roy CS, Verma P, Bhandari V (2012) A review on recent advances of enteric coating. IOSR J Pharm 2(6):05–11

    Google Scholar 

  33. Salam MA, Burk R (2017) Synthesis and characterization of multi-walled carbon nanotubes modified with octadecylamine and polyethylene glycol. Arab J Chem 10:S921–S927

    Article  CAS  Google Scholar 

  34. Jiang L, Gao L, Sun J (2003) Production of aqueous colloidal dispersions of carbon nanotubes. J Colloid Interface Sci 260:89–94

    Article  CAS  Google Scholar 

  35. Li ZF, Luo GH, Zhou WP, Wei F, Xiang R, Liu YP (2006) The quantitative characterization of the concentration and dispersion of multi-walled carbon nanotubes in suspension by spectrophotometry. Nanotechnology 17:3692–3698

    Article  CAS  Google Scholar 

  36. Alex AT, Joseph A, Shavi G, Rao JV, Udupa N (2016) Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery. Drug Deliv 23:1244–2153. https://doi.org/10.3109/10717544.2014.948643

    Article  CAS  Google Scholar 

  37. Habibizadeh M, Rostamizadeh K, Dalali N, Ramazani A (2016) Preparation and characterization of PEGylated multiwall carbon nanotubes as covalently conjugated and non-covalent drug carrier: a comparative study. Mater Sci Eng C. https://doi.org/10.1016/j.msec.2016.12.023

    Article  Google Scholar 

  38. Khan MA, Zafaryab M, Mehdi SH, Quadri J, Moshahid M, Rizvi A (2017) Characterization and carboplatin loaded chitosan nanoparticles for the chemotherapy against breast cancer in vitro studies. Int J Biol Macromol 97:115–122. https://doi.org/10.1016/j.ijbiomac.2016.12.090

    Article  CAS  Google Scholar 

  39. Guisado EP, Barrientos AA, Navarro SM, Josefat BS, Salguero PMF (2002) The antiproliferative activity of resveratrol results in apoptosis in MCF-7 but not in MDA-MB-231 human breast cancer cells: cell-specific alteration of the cell cycle. Biochem Pharmacol 64:1375–1386

    Article  Google Scholar 

  40. Sano M, Kamino A, Okamura J, Shinkai S (2001) Ring closure of carbon nanotubes. Science 293:1299

    Article  CAS  Google Scholar 

  41. Bonard JM, Stora T, Salvetat JP, Maier F, Stöckli T, Duschl C, Forró L, Heer WA, Châtelain A (1997) Purification and size-selection of carbon nanotubes. Adv Mater 9:827

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the Department of Science and Technology (DST-inspired), New Delhi (India), for funding this project.

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  1. Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India

    Suraj Sharma, Sweet Naskar & Ketousetuo Kuotsu

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  1. Suraj Sharma
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Correspondence to Ketousetuo Kuotsu.

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Sharma, S., Naskar, S. & Kuotsu, K. Metronomic chemotherapy of carboplatin-loaded PEGylated MWCNTs: synthesis, characterization and in vitro toxicity in human breast cancer. Carbon Lett. 30, 435–447 (2020). https://doi.org/10.1007/s42823-019-00113-0

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