Skip to main content
Log in

Biocompatible polymers coated on carboxylated nanotubes functionalized with betulinic acid for effective drug delivery

  • Delivery Systems
  • Original Research
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Chemically functionalized carbon nanotubes are highly suitable and promising materials for potential biomedical applications like drug delivery due to their distinct physico-chemical characteristics and unique architecture. However, they are often associated with problems like insoluble in physiological environment and cytotoxicity issue due to impurities and catalyst residues contained in the nanotubes. On the other hand, surface coating agents play an essential role in preventing the nanoparticles from excessive agglomeration as well as providing good water dispersibility by replacing the hydrophobic surfaces of nanoparticles with hydrophilic moieties. Therefore, we have prepared four types of biopolymer-coated single walled carbon nanotubes systems functionalized with anticancer drug, betulinic acid in the presence of Tween 20, Tween 80, polyethylene glycol and chitosan as a comparative study. The Fourier transform infrared spectroscopy studies confirm the bonding of the coating molecules with the SWBA and these results were further supported by Raman spectroscopy. All chemically coated samples were found to release the drug in a slow, sustained and prolonged fashion compared to the uncoated ones, with the best fit to pseudo-second order kinetic model. The cytotoxic effects of the synthesized samples were evaluated in mouse embryonic fibroblast cells (3T3) at 24, 48 and 72 h. The in vitro results reveal that the cytotoxicity of the samples were dependent upon the drug release profiles as well as the chemical components of the surface coating agents. In general, the initial burst, drug release pattern and cytotoxicity could be well-controlled by carefully selecting the desired materials to suit different therapeutic applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Tan JM, Arulselvan P, Fakurazi S, Ithnin H, Hussein MZ. A review on characterizations and biocompatibility of functionalized carbon nanotubes in drug delivery design. J Nanomater. 2014;. doi:10.1155/2014/917024.

    Google Scholar 

  2. Zheng X, Wang T, Jiang H, Li Y, Jiang T, Zhang J, Wang S. Incorporation of carvedilol into PAMAM-functionalized MWNTs as a sustained drug delivery system for enhanced dissolution and drug-loading capacity. Asian J Pharm Sci. 2013;8:278–86.

    Article  Google Scholar 

  3. Gaillard C, Duval M, Dumortier H, Bianco AJ. Carbon nanotube-coupled cell adhesion peptides are non-immunogenic: a promising step toward new biomedical devices. Pept Sci. 2011;17:139–42.

    Article  Google Scholar 

  4. Huang H, Yuan Q, Shah JS, Misra RDK. A new family of folate-decorated and carbon nanotube-mediated drug delivery system: synthesis and drug delivery response. Adv Drug Deliv Rev. 2011;63:1332–9.

    Article  Google Scholar 

  5. Kostarelos K, Lacerda L, Pastorin G, et al. Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell type. Nat Nanotechnol. 2007;2:108–13.

    Article  Google Scholar 

  6. Jos A, Pichardo S, Puerto M, Sánchez E, Grilo A, Cameán AM. Cytotoxicity of carboxylic acid functionalized single wall carbon nanotubes on the human intestinal cell line Caco-2. Toxicol Vitro. 2009;23:1491–6.

    Article  Google Scholar 

  7. Saxena RK, Williams W, Mcgee JK, Daniels MJ, Boykin E, Gilmour MI. Enhanced in vitro and in vivo toxicity of poly-dispersed acid-functionalized single-wall carbon nanotubes. Nanotoxicology. 2007;1:291–300.

    Article  Google Scholar 

  8. Rastogi R, Kaushal R, Tripathi SK, Sharma AL, Kaur I, Bharadwaj LM. Comparative study of carbon nanotube dispersion using surfactants. J Colloid Interf Sci. 2008;328:421–8.

    Article  Google Scholar 

  9. Berlin JM, Leonard AD, Pham TT, et al. Effective drug delivery, in vitro and in vivo, by carbon-based nanovectors noncovalently loaded with unmodified paclitaxel. ACS Nano. 2010;4:4621–36.

    Article  Google Scholar 

  10. Tan JM, Karthivashan G, Arulselvan P, Fakurazi S, Hussein MZ. Sustained release and cytotoxicity evaluation of carbon nanotube-mediated drug delivery system for betulinic acid. J Nanomater. 2014;. doi:10.1155/2014/862148.

    Google Scholar 

  11. Magrez A, Kasas S, Salicio V, Pasquier N, Seo JW, Celio M, Catsicas S, Schwaller B, Forró L. Cellular toxicity of carbon-based nanomaterials. Nano Lett. 2006;6(6):1121–5.

    Article  Google Scholar 

  12. Patočka J. Biologically active pentacyclic triterpenes and their current medicine signification. J Appl Biomed. 2003;10(3):7–12.

    Google Scholar 

  13. Sahoo RK, Biswas N, Guha A, Sahoo N, Kuotsu K. Nonionic surfactant vesicles in ocular delivery: innovative approaches and perspectives. Biomed Res Int. 2014;. doi:10.1155/2014/263604.

    Google Scholar 

  14. Kaur P, Shin MS, Joshi A, Kaur N, Sharma N, Park JS, Sekhon SS. Interactions between multiwall carbon nanotubes and poly(diallyl dimethylammonium) chloride: effect of the presence of a surfactant. J Phys Chem B. 2013;117:3161–6.

    Article  Google Scholar 

  15. Vinardell MP, Infante MR. The relationship between the chain length of non-ionic surfactants and their hemolytic action on human erythrocytes. Comp Biochem Physiol C. 1999;124:117–20.

    Article  Google Scholar 

  16. Kerwin BA. Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways. J Pharm Sci. 2008;97:2924–35.

    Article  Google Scholar 

  17. Kadajji VG, Betageri GV. Water soluble polymers for pharmaceutical applications. Polymers. 2011;3:1972–2009.

    Article  Google Scholar 

  18. Li C, Yang K, Zhang Y, et al. Highly biocompatible multi-walled carbon nanotube-chitosan nanoparticles hybrids as protein carriers. Acta Biomater. 2011;7:3070–7.

    Article  Google Scholar 

  19. Kong Z, Yu M, Cheng K, et al. Incorporation of chitosan nanospheres into thin mineralized collagen coatings for improving the antibacterial effect. Colloids Surf B. 2013;111:536–41.

    Article  Google Scholar 

  20. Kura AU, Hussein-Al-Ali SH, Hussein MZ, Fakurazi S. Preparation of tween 80-zn/al-levodopa-layered double hydroxides nanocomposite for drug delivery system. Sci World J. 2014;. doi:10.1155/2014/104246.

    Google Scholar 

  21. Dorniani D, Kura AU, Hussein-Al-Ali SH, Hussein MZ, Fakurazi S, Shaari AH, Ahmad Z. Release behavior and toxicity profiles towards leukemia (WEHI-3B) cell lines of 6-mercaptopurine-PEG-coated magnetite nanoparticles delivery system. Sci World J. 2014;. doi:10.1155/2014/972501.

    Google Scholar 

  22. Guo Z, Xiong J, Yang M, et al. Dispersion of nano-TiN powder in aqueous media. J Alloy Compd. 2010;493:362–7.

    Article  Google Scholar 

  23. Xiong J, Xiong S, Guo Z, Yang M, Chen J. Fan. Ultrasonic dispersion of nano TiC powders aided by tween 80 addition. Ceram Int. 2012;38:1815–21.

    Article  Google Scholar 

  24. Borges AC, Jayakrishnan A, Bourban PE, Plummer CJG, Pioletti DP, Månson JAE. Synthesis and photopolymerization of tween 20 methacrylate/N-vinyl-2-pyrrolidone blends. Mater Sci Eng C. 2012;32:2235–41.

    Article  Google Scholar 

  25. Shameli K, Ahmad M, Jazayer SD, et al. Synthesis and characterization of polyethylene glycol mediated silver nanoparticles by the green method. Int J Mol Sci. 2012;13:6639–50.

    Article  Google Scholar 

  26. Xu XH, Ren GL, Cheng J, Liu Q, Li DGJ. Layer by layer self-assembly immobilization of glucose oxidase onto chitosan-graft-polyaniline polymers. Mater Sci. 2006;41:3147–9.

    Article  Google Scholar 

  27. Ge B, Tan Y, Xie Q, Ma M, Yao S. Preparation of chitosan-dopamine-multiwalled carbon nanotubes nanocomposite for electrocatalytic oxidation and sensitive electroanalysis of NADH. Sensors Actuator B. 2009;137:547–54.

    Article  Google Scholar 

  28. Liu AH, Honma I, Zhou HS. Electrochemical biosensor based on protein-polysaccharide hybrid for selective detection of nanomolar dopamine metabolite of 3,4-dihydroxiphenylacetic acid (DOPAC). Eletrochem Commun. 2005;7:233–6.

    Article  Google Scholar 

  29. Lei XW, Ni QQ, Shi JX, Natsuki T. Radial breathing mode of carbon nanotubes subjected to axial pressure. Nanoscale Res Lett. 2011;6:492–7.

    Article  Google Scholar 

  30. Bokobza L, Zhang J. Raman spectroscopic characterization of multiwall carbon nanotubes and of composites. Exp Polym Lett. 2012;6:601–8.

    Article  Google Scholar 

  31. Ponnamma D, Sung SH, Hong JS, Ahn KH, Varughese KT, Thomas S. Influence of non-covalent functionalization of carbon nanotubes on the rheological behavior of natural rubber latex nanocomposites. Eur Polym J. 2014;53:147–59.

    Article  Google Scholar 

  32. Nowacki M, Wiśniewski M, Werengowska-Ciećwierz K, et al. New application of carbon nanotubes in haemostatic dressing filled with anticancer substance. Biomed Pharmacother. 2015;69:349–54.

    Article  Google Scholar 

  33. Yeo Y, Park K. Control of encapsulation efficiency and initial burst in polymeric microparticle systems. Arch Pharm Res. 2004;27:1–12.

    Article  Google Scholar 

  34. Mehta RC, Thanoo BC, DeLuca PP. Peptide containing microspheres from low molecular weight and hydrophilic poly(d,l-lactide-co-glycolide). J Control Release. 1996;41:249–57.

    Article  Google Scholar 

  35. Benyettou F, Hardouin J, Lecouvey M, Jouni H, Mottle L. PEGylated versus non-PEGylated γFe2O3@alendronate nanoparticles. J Bioanal Biomed. 2012;4:039–45.

    Google Scholar 

  36. Muzzalupo R, Tavano L, Cassano R, Trombino S, Cilea A, Picci N. Colon-specific devices based on methacrylic functionalized tween monomer networks: swelling studies and in vitro drug release. Eur Polym J. 2010;46:209–16.

    Article  Google Scholar 

  37. Muzzarelli R, Baldassarre V, Conti F, Ferrara P, Biagini G, Gazzanelli G, Vasi V. Biological activity of chitosan: ultrastructural study. Biomaterials. 1988;9:247–52.

    Article  Google Scholar 

  38. Mehta SK, Kaur G, Bhasin KK. Tween-embedded microemulsions—physicochemical and spectroscopic analysis for antitubercular drugs. AAPS PharmSciTech. 2010;11(1):143–53.

    Article  Google Scholar 

  39. Hussein-Al-Ali SH, Arulselvan P, Fakurazi S, Hussein MZ. The in vitro therapeutic activity of betulinic acid nanocomposite on breast cancer cells (MCF-7) and normal fibroblast cell (3T3). J Mater Sci. 2014;49:8171–82.

    Article  Google Scholar 

  40. Ratanajiajaroen P, Watthanaphanit A, Tamura H, Tokura S, Rujiravanit R. Release characteristic and stability of curcumin incorporated in β–chitin non-woven fibrous sheet using tween 20 as an emulsifier. Eur Polym J. 2012;48:512–23.

    Article  Google Scholar 

  41. Ho YS, McKay G. A comparison of chemisorption kinetic models applied to pollutant removal on various sorbents. Process Saf Environ. 1998;76:332–40.

    Article  Google Scholar 

  42. Ren W, Tian G, Jian S, et al. TWEEN coated NaYF4: Yb, Er/NaYF4 core/shell upconversion nanoparticles for bioimaging and drug delivery. RSC Adv. 2012;2:7037–41.

    Article  Google Scholar 

  43. Hu X, Wang Y, Peng B. Chitosan-capped mesoporous silica nanoparticles as pH-responsive nanocarriers for controlled drug release. Chem Asian J. 2014;9:319–27.

    Article  Google Scholar 

  44. Herold DA, Rodeheaver GT, Bellamy WT, Fitton LA, Bruns DE, Edlich RF. Toxicity of topical polyethylene glycol. Toxicol Appl Pharm. 1982;65:329–35.

    Article  Google Scholar 

  45. Beasley VR, Buck WB. Acute ethylene glycol toxicosis: a review. Vet Human Toxicol. 1980;22:255–63.

    Google Scholar 

  46. Fruijtier-Pölloth C. Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products. Toxicology. 2005;214:1–38.

    Article  Google Scholar 

Download references

Acknowledgments

This study is financially supported by the Ministry of Education of Malaysia (MOE) under the PUTRA-IPB grant No. GP-IPB/2013/9425800. Author Julia M. Tan is also grateful to MOE for providing MyPhD scholarship under the MyBrain15 program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mohd Zobir Hussein.

Ethics declarations

Conflicts of Interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, J.M., Karthivashan, G., Abd Gani, S. et al. Biocompatible polymers coated on carboxylated nanotubes functionalized with betulinic acid for effective drug delivery. J Mater Sci: Mater Med 27, 26 (2016). https://doi.org/10.1007/s10856-015-5635-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10856-015-5635-8

Keywords

Navigation