Skip to main content

Advertisement

Log in

Halloysite Nanotubes for Nanomedicine: Prospects, Challenges and Applications

  • Published:
BioNanoScience Aims and scope Submit manuscript

Abstract

Recently, naturally occurring and abundantly available halloysite nanoclay has emerged as a nanomaterial carrier system suitable for both controlled and sustained delivery. These aluminosilicate tubes of 50-nm diameter, with outer silica and inner alumina layers, possess a tubular structure, with excellent features such as large aspect ratio, good biocompatibility, and high mechanical strength entails them to be suitable for drug delivery. The unique features of these nanotubes are the ability to load DNA and enzyme due to opposite charges on both inner and outer surfaces which allow selective drug loading on both surfaces. This review article emphasizes on the drug loading techniques with release characteristics and some important applications in biomedical, environmental fields, and different types of medication. Being most versatile, these nanotubes can be used widely as a carrier system for enzyme bases and different types of the nucleus which can be a most promising step for novel drug delivery systems.

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

Similar content being viewed by others

References

  1. Tjong, S. C. (2006). Structural and mechanical properties of polymer nanocomposites. Materials Science and Engineering, 53(3–4), 73–197.

    Google Scholar 

  2. Kashiwagi, T., Du, F., Douglas, J. F., Winey, K. I., & Harris Jr., R. H. (2005). Nanoparticle networks reduce the flammability of polymer nanocomposites. Nature Materials, 4(12), 928–933.

    Google Scholar 

  3. Ramanathan, T., Abdala, A., Stankovich, S., Dikin, D., Herrera-Alonso, M., Piner, R., & Adamson, D. (2008). Functionalized graphene sheets for polymer nanocomposites. Nature Nanotechnology, 3(6), 327–331.

    Google Scholar 

  4. Lvov, Y., & Abdullayev, E. (2013). Functional polymer–clay nanotube composites with sustained release of chemical agents. Progress in Polymer Science, 38(10–11), 1690–1719.

    Google Scholar 

  5. Liu, M., Jia, Z., Jia, D., & Zhou, C. (2014). Recent advance in research on halloysite nanotubes- polymer nanocomposite. Progress in Polymer Science, 39(8), 1498–1525.

    Google Scholar 

  6. Brindley, G. W. (1955). Structural mineralogy of clays. Clays and Clay Technology, 169(8), 33–44.

    Google Scholar 

  7. Hanif, M., Jabbar, F., Sharif, S., Assas, G., Farooq, A., & Aziz, M. (2016). Halloysite nanotubes as a new drug-delivery system: A review. Clay Minerals, 51(2), 469–477.

    Google Scholar 

  8. Brindley, G. W., & Robinson, K. (1948). X-ray studies of halloysite and metahalloysite, I: The structure of metahalloysite, an example of random layer lattice. Mineralogical Magazine, 28(203), 393–406.

    Google Scholar 

  9. Briggati, M. F., Galan, E., & Theng, B. K. G. (2006). Structures and mineralogy of clay minerals. In F. Bergaya, B. K. G. Theng, & G. Lagaly (Eds.), Handbook of Clay Science (pp. 19–86). Amsterdam, 1: Elsevier.

    Google Scholar 

  10. Wilson, I., & Keeling, J. (2016). Global occurrence geology and characteristics of tubular halloysite deposits. Clay Minerals, 51(3), 309–324.

    Google Scholar 

  11. Churchman, G. J., & Theng, B. K. G. (1984). Interactions of halloysites with amides: Mineralogical factors affecting complex formation. Clay Minerals, 19(2), 161–175.

    Google Scholar 

  12. Churchman, G. J., & Theng, B. K. G. (2006). Clay research in Australia and New Zealand. Applied Clay Science, 1, 625–675.

    Google Scholar 

  13. Perruchot, A., Dupuis, C., Brouard, E., Nicaise, D., & Ertus, R. (1997). Halloysitekarstique: comparaison des gisements types de Wallonie (Belgique) et du Perigord (France). Clay Minerals, 32(2), 271–287.

    Google Scholar 

  14. Kloprogge, J. T., & Frost, R. L. (1999). Raman microprobe spectroscopy of hydrated halloysite from a neogenecryptokarst from Southern Belgium. Journal of Raman Spectroscopy, 30, 1079–1085.

    Google Scholar 

  15. Papoulis, D., Komarneni, S., & Panagiotaras, D. (2014). Geochemistry of halloysite-7 Å formation from plagioclase in trachyandesite rocks from Limnos Island, Greece. Clay Minerals, 49(1), 75–89.

    Google Scholar 

  16. Veerabadran, N. G., Mongayt, D., Torchilin, V., Price, R. R., & Lvov, Y. M. (2009). Organized shell on clay nanotubes for controlled release of macromolecules. Macromolecular Rapid Communications, 30(2), 99–103.

    Google Scholar 

  17. Abdullayev, E., & Lvov, Y. (2011). Halloysite clay nanotubes for controlled release of protective agents. Journal of Nanoscience and Nanotechnology, 11(11), 10007–10026.

    Google Scholar 

  18. Du, M., Guo, B., & Jia, D. (2010). Newly emerging applications of halloysite nanotubes: A review. Polymer International, 59, 574–582.

    Google Scholar 

  19. Chao, C., Liu, J., Wang, J., Zhang, Y., Zhang, B., Zhang, Y., et al. (2013). Surface modification of halloysite nanotubes with dopamine for enzyme immobilization. ACS Applied Materials & Interfaces, 5(21), 10559–10564.

    Google Scholar 

  20. Lvov, Y., Wang, W., Zhang, L., & Fakhrullin, R. (2016). Halloysite clay nanotubes for loading and sustained release of functional compounds. Advanced Materials, 28(6), 1227–1250.

    Google Scholar 

  21. Abdullayev, E., Price, R., Shchukin, D., & Lvov, Y. (2009). Halloysite tubes as nanocontainers for anticorrosion coating with benzotriazole. ACS Applied Materials & Interfaces, 1, 1437–1443.

    Google Scholar 

  22. Berthier, P. (2004). Analyse de l’halloysit. Annales de Chimie Physique, 32, 332–335.

    Google Scholar 

  23. Bates, T. F., Hildebrand, F. A., & Swineford, A. (1950). Morphology and structure of endellite and halloysite. American Mineralogist, 35, 463–484.

    Google Scholar 

  24. Joussein, E., Petit, S., Churchman, J., Theng, B., Righi, D., & Delvaux, B. (2005). Halloysite clay minerals–a review. Clay Minerals, 40(4), 383–426.

    Google Scholar 

  25. Handge, U. A., Hedicke-Höchstötter, K., & Altstädt, V. (2010). Composites of polyamide 6 and silicate nanotubes of the mineral halloysite: Influence of molecular weight on thermal, mechanical and rheological properties. Polymer, 51, 2690–2699.

    Google Scholar 

  26. Liu, M., Zhang, Y., & Zhou, C. (2013). Nanocomposites of halloysite and polylactide. Applied Clay Science, 75, 52–59.

    Google Scholar 

  27. Veerabadran, N. G., Price, R. R., & Lvov, Y. M. (2007). Clay nanotubes for encapsulation and sustained release of drugs. NANO: Brief Reports and Reviews, 2, 115–120.

    Google Scholar 

  28. Abdullayev, E., Joshi, A., Wei, W., Zhao, Y., & Lvov, Y. (2012). Enlargement of halloysite clay nanotube lumen by selective etching of aluminum oxide. American Chemical Society Nano, 6(8), 7216–7226.

    Google Scholar 

  29. Riela, S., Massaro, M., Colleti, C. G., Bommarito, A., Giordano, C., Noto, R., Poma, P., & Lazzara, G. (2014). Development and characterization of co-loaded curcumin/triazole halloysite systems and evaluation of their potential anticancer activity. International Journal of Pharmaceutics, 475, 613–623.

    Google Scholar 

  30. Massaro, M., Amorati, R., Cavallaro, G., Guernelli, S., Lazzara, G., Milioto, S., Noto, R., Poma, P., & Riela, S. (2016). Direct chemical grafted curcumin on halloysite nanotubes as dual-responsive prodrug for pharmacological applications. Colloids and Surfaces B: Biointerfaces, 140, 505–513.

    Google Scholar 

  31. Price, R. R., Gaber, B. P., & Lvov, Y. (2001). In-vitro release characteristics of tetracycline HCL, khellin and nicotinamide adenine dineculeotide from halloysite; a cylindrical mineral. Journal of Microencapsulation, 18(6), 713–722.

    Google Scholar 

  32. Shi, Y., Tian, Z., Zhang, Y., Shen, H., & Jia, N. (2011). Functionalized halloysite nanotube-based for intracellular delivery of antisense oligonucleotides. Nanoscale Research Letters, 6(1), 1–7.

    Google Scholar 

  33. Yah, W. O., Xu, H., Soejima, H., Ma, W., Lvov, Y., & Takahara, A. (2012). Biomimetic dopamine derivative for selective polymer modification of halloysite nanotube lumen. Journal of the American Chemical Society, 134(29), 12134–12137.

    Google Scholar 

  34. Cavallaro, G., Lazzara, G., & Milioto, S. (2012). Exploiting the colloidal stability and solubilization ability of clay nanotubes/ionic surfactant hybrid nanomaterials. The Journal of Physical Chemistry C, 116(41), 21932–21938.

    Google Scholar 

  35. Patel, S., Jammalamadaka, U., Sun, L., Tappa, K., & Mills, D. K. (2016). Sustained release of antibacterial agents from doped halloysite nanotubes. Bioengineering, 3(1), 1–14.

    Google Scholar 

  36. Fan, L., Zhang, J., & Wang, A. (2013). In situ generation of sodialginate/hydroxyapatite/halloysite nanotubes composite hydrogel beads as drug-controlled release matrices. Journal of Materials Chemistry B, 45, 6261–6270.

    Google Scholar 

  37. Massaro, M., Colletti, C. G., Noto, R., Riela, S., Poma, P., Guernelli, S., Parisi, F., Milioto, S., & Lazzara, G. (2015). Pharmaceutical properties of supramolecular assembly of co-loaded cardanol/triazole-halloysite systems. International Journal of Pharmaceutics, 478(2), 476–485.

    Google Scholar 

  38. Tully, J., Yendluri, R., & Lvov, Y. (2016). Halloysite clay nanotubes for enzyme immobilization. Biomacromolecules, 17(2), 615–621.

    Google Scholar 

  39. Lun, H., Ouyang, J., & Yang, H. (2014). Natural halloysite nanotubes modified as an aspirin carrier. The Royal Society of Chemistry Advances, 4, 44197–44202.

    Google Scholar 

  40. Sun, J., Yendluri, R., Lui, K., Guo, Y., Lvov, Y., & Yan, X. (2017). Enzyme-immobilized clay nanotubes chitosan membranes with sustained biocatalytic activities. Physical Chemistry Chemical Physics, 19(1), 562–567.

    Google Scholar 

  41. Dzamukova, M. R., Naumenko, E. A., Lvov, Y. M., & Fakhrullin, R. F. (2015). Enzyme-activated intracellular drug delivery with tubule clay nano formulation. Scientific Reports, 5, 10560–10566.

    Google Scholar 

  42. Lazzara, G., Riela, S., & Fakhrullin, R. F. (2007). Clay-based drug delivery systems: What does the future hold? NANO: Brief Reports and Reviews, 2, 115–120.

    Google Scholar 

  43. Liu, M., Guo, B., Du, M., Cai, X., & Jia, D. (2007). Properties of halloysite nanotube–epoxy resin hybrids and the interfacial reactions in the systems. Nanotechnology, 18(45), 455703.

    Google Scholar 

  44. Carroll, D., & Starkey, H. C. (1971). Reactivity of clay minerals with acids and alkalis. Clay Minerals, 19(5), 321–333.

    Google Scholar 

  45. Korsmeyer, R. W., Gurny, R., Doelker, E., Buri, P., & Peppas, N. A. (1983). Mechanisms of solute release from porous hydrophilic polymers. International Journal of Pharmaceutics, 15(1), 25–35.

    Google Scholar 

  46. Abdullayev, E., & Lvov, Y. (2013). Halloysite clay nanotubes as a ceramic “skeleton” for functional biopolymer composites with sustained drug release. Journal of Materials Chemistry B, 1, 2894–2903.

    Google Scholar 

  47. Wei, W., Minullina, R., Abdullayev, E., Fakhrullin, R., Mills, D., & Lvov, Y. (2014). Enhanced efficiency of antiseptics with sustained release from clay nanotubes. RCS Advances, 4, 488–494.

    Google Scholar 

  48. Wei, W., Abdullayev, E., Hollister, A., Lvov, Y., & Mills, D. (2012). Clay nanotube/poly(methyl methacrylate) bone cement composite with sustained antibiotic release. Macromolecular Materials and Engineering, 297(7), 645–653.

    Google Scholar 

  49. Aguzzi, C., Viseras, C., Cerezo, P., Salcedo, I., Sa’nchez-Espejo, R., & Valenzuela, C. (2013). Release kinetics of 5-aminosalicylic acid from halloysite. Colloidal Surface B Biointerfaces, 105, 75–80.

    Google Scholar 

  50. Lvov, Y., & Price, R. (2008). Halloysite nano tubules a novel substrate for the controlled delivery of bioactive molecules. In E. Ruiz-Hitzky, K. Ariga, & Y. Lvov (Eds.), Bio-inorganic hybrid nanomaterials (pp. 440–478). London: Wiley.

    Google Scholar 

  51. Vergaro, V., Abdullayev, E., Lvov, Y. M., Zeitoun, A., Cingolani, R., Rinaldi, R., & Leporatti, S. (2010). Cytocompatibility and uptake of halloysite clay nanotubes. Biomacromolecules, 11(3), 820–826.

    Google Scholar 

  52. Liu, M., Chang, Y., Yang, J., You, Y., He, R., Chen, T., & Zhou, C. (2016). Functionalized Halloysite nanotube by chitosan grafting for drug delivery of curcumin to achieve enhanced anticancer efficacy. Journal of Materials Chemistry B, 4(13), 2253–2263.

    Google Scholar 

  53. Hughes, A. D., & King, M. R. (2010). Use of naturally occurring halloysite nanotubes for enhanced capture of flowing cells. Langmuir, 26(14), 12155–12164.

    Google Scholar 

  54. He, R., Liu, M., Shen, Y., Long, Z., & Zhou, C. (2017). Large-area assembly of halloysite nanotubes for enhancing the capture of tumor cells. Journal of Materials Chemistry B, 5(9), 1712–1723.

    Google Scholar 

  55. Wu, Y., Yang, J., & Gao, H. (2017). Folate conjugated halloysite nanotubes an efficient drug carrier deliver doxorubicin fir targeted therapy of breast cancer. ACS Applied Nanomaterials, 1(2), 595–608.

    Google Scholar 

  56. Long, Z., Zhang, J., Shen, Y., & Liu, M. (2017). Polyethyleneimine grafted short halloysite nanotubes for gene delivery. Materials Science and Engineering: C, 81, 224–235.

    Google Scholar 

  57. Zhao, M., & Liu, P. (2008). Adsorption behavior of methylene blue on halloysite nanotubes. Microporous and Mesoporous Materials, 112(1–3), 419–424.

    Google Scholar 

  58. Peng, Q., Liu, M., Zheng, J., & Zhou, C. (2015). Adsorption of dyes in aqueous solutions by chitosan–halloysite nanotubes composite hydrogel beads. Microporous and Mesoporous Materials, 201, 190–201.

    Google Scholar 

  59. Shchukin, D. G., Sukhorukov, G. B., Price, R. R., & Lvov, Y. M. (2005). Halloysite nanotubes as biomimetic nanoreactors. Small, 1(5), 510–513.

    Google Scholar 

  60. Abdullayev, E., Sakakibara, K., Okamoto, K., Wei, W., Ariga, K., & Lvov, Y. (2011). Natural tubule clay template synthesis of silver nanorods for antibacterial composite coating. ACS Applied Materials & Interfaces, 3(10), 4040–4046.

    Google Scholar 

  61. Rostamzadeh, T., Islam Khan, M. S., Riché, K., Lvov, Y. M., Stavitskaya, A. V., & Wiley, J. B. (2017). Rapid and controlled in situ growth of noble metal nanostructures within halloysite clay nanotubes. Langmuir, 33(45), 13051–13059.

    Google Scholar 

  62. Makaremi, M., Pasbakhsh, P., Cavallaro, G., Lazzara, G., Aw, Y. K., Lee, S. M., & Milioto, S. (2017). Effect of morphology and size of halloysite nanotubes on functional pectin bio nanocomposites for food packaging applications. ACS Applied Materials & Interfaces, 9(20), 17476–17488.

    Google Scholar 

  63. Zeng, G., He, Y., Zhan, Y., Zhang, L., Shi, H., & Yu, Z. (2016). Preparation of a novel poly (vinylidene fluoride) ultrafiltration membrane by incorporation of 3-aminopropyltriethoxysilane-grafted halloysite nanotubes for oil/water separation. Industrial and Engineering Chemistry Research, 55(6), 1760–1767.

    Google Scholar 

  64. Riedlinger, M., & Corkery, R. (2007). Cosmetic skincare applications employing mineral-derived tubules for controlled release, in Google patents. United States: Natural nanotechnology Inc..

    Google Scholar 

  65. Kurczewska, J., Pecyna, P., Ratajczak, M., Gajecka, M., & Schroeder, G. (2017). Halloysite nanotubes as carriers of Vancomycin in alginate-based wound dressing. Saudi Pharmaceutical Journal, 25(6), 911–920.

    Google Scholar 

  66. Yendluri, R., Lvov, Y., Devilliers, M., Vinokurov, V., Naumenko, E., Tarasova, E., & Fakhurullin, R. (2017). Paclitaxel encapsulated in halloysite clay nanotubes for intestinal and intracellular delivery. Journal of Pharmaceutical Sciences, 106(10), 3131–3139.

    Google Scholar 

  67. Tang, X., Li, L., Shen, B., & Wang, C. (2013). Halloysite-nanotubes supported FeNi alloy nanoparticles for catalytic decomposition of toxic phosphine gas into yellow phosphorus and hydrogen. Chemosphere, 91(9), 1368–1373.

    Google Scholar 

  68. Liu, P., & Zhao, M. (2009). Applied surface science silver nanoparticle supported on Halloysite nanotubes catalyzed reduction of 4-nitrophenol (4-NP). Applied Surface Science, 255(7), 3989–3993.

    Google Scholar 

  69. Zhang, A., Liu, S., Yan, K., Ye, Y., & Chen, X. (2014). Facile preparation of MnFe2O4/Halloysite nanotubular encapsulates with enhanced magnetic and electromagnetic performances. RSC Advances, 4(26), 13565–13568.

    Google Scholar 

  70. Zhang, Y., Chen, Y., Zhang, H., Zhang, B., & Liu, J. (2013). Potent antibacterial activity of a novel silver nanoparticle-halloysite nanotube nanocomposite powder. Journal of Inorganic Biochemistry, 118, 59–64.

    Google Scholar 

  71. Marney, D. C. O., Russell, L. J., Wu, D. Y., Nguyen, T., Cramm, D., Rigopoulos, N., & Wright, N. (2008). The suitability of halloysite nanotubes as a fire retardant for nylon 6. Polymer Degradation and Stability, 93, 1971–1978.

    Google Scholar 

  72. Kamble, R., Ghag, M., Gaikawad, S., & Panda, B. K. (2012). Halloysite nanotubes and applications: A review. Journal of Advanced Scientific Research, 3(2), 25–29.

    Google Scholar 

  73. Thakur, P., Kool, A., Bagchi, B., Das, S., & Nandy, P. (2014). Enhancement of β phase crystallization and dielectric behavior of kaolinite/halloysite modified poly(vinylidenefluoride) thin films. Applied Clay Science, 99, 149–159.

    Google Scholar 

  74. Zhou, X., Li, K., Tu, R., Yi, J., Xie, Q., & Jiang, X. (2016). A modelling study of the multiphase leakage flow from pressurised CO2 pipeline. Journal of Hazardous Materials, 306, 286–294.

    Google Scholar 

  75. Zhang, L., Wang, T., & Liu, P. (2008). Polyaniline-coated halloysite nanotubes via in-situ chemical polymerization. Applied Surface Science, 255, 2091–2097.

    Google Scholar 

  76. Levis, S. R., & Deasy, P. B. (2002). Characterisation of halloysite for use as a microtubular drug delivery system. International Journal of Pharmaceutics, 243(1–2), 125–134.

    Google Scholar 

  77. Zhao, X., Fu, X., & Wan, Q. (2017). The toxicity evaluation of one dimensional nanoparticles using caenorhabditis elegance: A comparative study of HNT and chitin nanocrystals. ACS Sustainable Chemistry & Engineering, 7(23), 18965–18975.

    Google Scholar 

  78. Long, Z., Wu, Y. P., Gao, H. Y., Zhang, J., & He, R. R. (2018). Invivo toxicity evaluation of HNT. Journal of Materials Chemistry B, 6(44), 7204–7216.

    Google Scholar 

Download references

Acknowledgements

The authors are grateful to the Pranveer Singh Institute of Technology, Department of Pharmacy, Kanpur, India, for the support and facilities during preparation of manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Swatantra Kumar Singh Kushwaha.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interest, financial or otherwise.

Research Involving Humans and Animals Statement

This review does not contain any studies with animal/human subjects by any of the authors.

Informed Consent

None.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kushwaha, S.K.S., Kushwaha, N., Pandey, P. et al. Halloysite Nanotubes for Nanomedicine: Prospects, Challenges and Applications. BioNanoSci. 11, 200–208 (2021). https://doi.org/10.1007/s12668-020-00801-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12668-020-00801-6

Keywords

Navigation