Implementation of a Simulation Model of the Controlled Release of Molecular Species from Halloysite Nanotubes


In this work a three-dimensional, time-quantified Monte Carlo model that efficiently describes diffusion through and from nanotubes is implemented. Controlled delivery from Halloysite Nano-tubes (HNT) is modeled based on interactions between the HNT’s inner wall and the nanoparticles (NPs) and among NPs themselves. The model was validated using published experimental data. The validated model is then used to study the effect of multiples parameter like HNT diameter and length, particle charge, and ambient temperature on the release of encapsulated NPs. The results show that release profiles depend on the size distribution of the HNT batch used for the experiment, as delivery is sensitive to HNT lumen and length. A very good agreement with the experiment is observed when a weighted average release profile is compared to the experimental profile. Although the NP dynamics is temperature-dependent, the effect is minimum within the range of temperatures relevant to biomedical applications, but will be relevant for other applications at temperatures significantly different from room temperature. This model can be used to predict the best conditions for a particular delivery need.

Share and Cite:

Elumalai, D. , Lvov, Y. and Derosa, P. (2015) Implementation of a Simulation Model of the Controlled Release of Molecular Species from Halloysite Nanotubes. Journal of Encapsulation and Adsorption Sciences, 5, 74-92. doi: 10.4236/jeas.2015.51006.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Jorio, A., Dresselhaus, G. and Dresselhaus, M.S. (2008) Carbon Nanotubes: Advanced Topics in the Synthesis, Structure, Properties and Applications. Springer, New York.
[2] Suh, Y.J., Kil, D.S., Chung, K.S., Abdullayev, E., Lvov, Y.M. and Mongayt, D. (2011) Natural Nanocontainer for the Controlled Delivery of Glycerol as a Moisturizing Agent. Journal of Nanoscience and Nanotechnology, 11, 661-665.
[3] Vergaro, V., Abdullayev, E., Lvov, Y.M., Zeitoun, A., Cingolani, R., Rinaldi, R. and Leporatti, S. (2010) Cytocompatibility and Uptake of Halloysite Clay Nanotubes. Biomacromolecules, 11, 820-826.
[4] Veerabadran, N., Mongayt, D., Torchilin, V., Price, R. and Lvov, Y. (2009) Organised Shells on Clay Nanotubes for Controlled Release of Macromolecules. Macromolecular Rapid Communications, 30, 99-103.
[5] Shchukin, D., Price, R., Sukhorukov, G. and Lvov, Y. (2005) Halloysite Nanotubes as Biomimetic Nanoreactors. Small, 1, 510-513.
[6] Price, R., Gaber, B. and Lvov, Y. (2001) In-Vitro Release Characteristics of Tetracycline HCl, Khellin and Nicotinamide Adenine Dineculeotide from Halloysite; a Cylindrical Mineral. Journal of Microencapsulation, 18, 713-722.
[7] Lvov, Y.M., Shchukin, D., Mohwald, H. and Price, R. (2008) Halloysite Clay Nanotubes for Controlled Release of Protective Agents. ACS Nano, 2, 814-820.
[8] Lvov, Y., Ariga, K., Ichinose, I. and Kunitake, T. (1996) Formation of Ultrathin Multilayer and Hydrated Gel from Montmorillonite and Linear Polycations. Langmuir, 12, 3038-3044.
[9] Kommireddy, D., Ichinose, I., Lvov, Y. and Mills, D. (2005) Nanoparticle Multilayers: Surface Modification for Cell Attachment and Growth. Journal of Biomedical Nanotechnology, 1, 286-290.
[10] Abdullayev, E., Price, R., Shchukin, D. and Lvov, Y. (2009) Halloysite Tubes as Nanocontainers for Anticorrosion Coating with Benzotriazole. ACS Applied Materials & Interfaces, 1, 1437-1443.
[11] Veerabadran, N.G., Price, R.R. and Lvov, Y.M. (2007) Clay Nanotubes for Encapsulation and Sustained Release of Drugs. NANO, 2, 115.
[12] Prow, T.W., Kotov, N.A., Lvov, Y.M., Rijnbrand, R. and Leary, J.F. (2004) Nanoparticles, Molecular Biosensors, and Multispectral Confocal Microscopy. Journal of Molecular Histology, 35, 555-564.
[13] Vergaro, V., Scarlino, F., Bellomo, C., Rinaldi, R., Vergara, D., Maffia, M., et al. (2011) Drug-Loaded Polyelectrolyte Microcapsules for Sustained Targeting of Cancer Cells. Advanced Drug Delivery Reviews, 63, 847-864.
[14] Abdullayev, E., Sakakibara, K., Okamoto, K., Wei, W., Ariga, K. and Lvov, Y. (2011) Natural Tubule Clay Template Synthesis of Silver Nanorods for Antibacterial Composite Coating. ACS Applied Materials & Interfaces, 3, 4040-4046.
[15] Abdullayev, E. and Lvov, Y.M. (2011) Halloysite Clay Nanotubes for Controlled Release of Protective Agents. Journal of Nanoscience and Nanotechnology, 11, 10007-10026.
[16] Zhai, R., Zhang, B., Liu, L., Xie, Y., Zhang, H. and Liu, J. (2010) Immobilization of Enzyme Biocatalyst on Natural Halloysite Nanotubes. Catalysis Communications, 12, 259-263.
[17] Levis, S.R. and Deasy, P.B. (2003) Use of Coated Microtubular Halloysite for the Sustained Release of Diltiazem Hydrochloride and Propranolol Hydrochloride. International Journal of Pharmaceutics, 253, 145-157.
[18] Levis, S.R. and Deasy, P.B. (2002) Characterisation of Halloysite for Use as a Microtubular Drug Delivery System. International Journal of Pharmaceutics, 243, 125-134.
[19] Kelly, H.M., Deasy, P.B., Ziaka, E. and Claffey, N. (2004) Formulation and Preliminary in Vivo Dog Studies of a Novel Drug Delivery System for the Treatment of Periodontitis. International Journal of Pharmaceutics, 274, 167-183.
[20] Li, G.L., Zheng, Z., Möhwald, H. and Shchukin, D.G. (2013) Silica/Polymer Double-Walled Hybrid Nanotubes: Synthesis and Application as Stimuli-Responsive Nanocontainers in Self-Healing Coatings. ACS Nano, 7, 2470-2478.
[21] Abdullayev, E. and Lvov, Y. (2010) Clay Nanotubes for Corrosion Inhibitor Encapsulation: Release Control with End Stoppers. Journal of Materials Chemistry, 20, 6681-6687.
[22] Zhao, Y., Abdullayev, E., Vasiliev, A. and Lvov, Y. (2013) Halloysite Nanotubule Clay for Efficient Water Purification. Journal of Colloid and Interface Science, 406, 121-129.
[23] Cavallaro, G., Donato, D.I., Lazzara, G. and Milioto, S. (2011) Films of Halloysite Nanotubes Sandwiched between Two Layers of Biopolymer: From the Morphology to the Dielectric, Thermal, Transparency, and Wettability Properties. The Journal of Physical Chemistry C, 115, 20491-20498.
[24] Hashemifard, S.A., Ismail, A.F. and Matsuura, T. (2011) Mixed Matrix Membrane Incorporated with Large Pore Size Halloysite Nanotubes (HNT) as Filler for Gas Separation: Experimental. Journal of Colloid and Interface Science, 359, 359-370.
[25] Macevan, D.M.C. (1946) Halloysite-Organic Complexes. Nature, 157, 159-160.
[26] Liu, W., Chaurand, P., Di Giorgio, C., De Méo, M., Thill, A., Auffan, M., et al. (2012) Influence of the Length of Imogolite-Like Nanotubes on Their Cytotoxicity and Genotoxicity toward Human Dermal Cells. Chemical Research in Toxicology, 25, 2513-2522.
[27] Rasul, J.S. (2004) Chip on Paper Technology Utilizing Anisotropically Conductive Adhesive for Smart Label Applications. Microelectronics Reliability, 44, 135-140.
[28] Joussein, E., Petit, S., Churchman, J., Theng, B., Righi, D. and Delvaux, B. (2005) Halloysite Clay Minerals—A Review. Clay Minerals, 40, 383-426.
[29] Tari, G., Bobos, I., Gomes, C. and Ferreira, J. (1999) Modification of Surface Charge Properties during Kaolinite to Halloysite-7Å Transformation. Journal of Colloid and Interface Science, 210, 360-366.
[30] Burke, T.G., Singh, A. and Yager, P. (1987) Entrapment of 6-Carboxyfluorescein within Cylindrical Phospholipid Microstructures. Annals of the New York Academy of Sciences, 507, 330-333.
[31] Kamble, R., Ghag, M., Gaikawad, S. and Panda, B.K. (2012) Halloysite Nanotubes and Applications: A Review. Journal of Advanced Scientific Research, 3, 25-59.
[32] Yang, Y., He, Q., Duan, L. and Li, J.B. (2007) Assembled Alginate/Chitosan Nanotubes for Biological Application. Biomaterials, 18, 3083-3090.
[33] Ariga, K., Lvov, Y.M., Kawakami, K., Ji, Q. and Hill, J.P. (2011) Layer-by-Layer Self-Assembled Shells for Drug Delivery. Advanced Drug Delivery Reviews, 63, 762-771.
[34] Liu, P. and Zhao, M. (2009) Silver Nanoparticle Supported on Halloysite Nanotubes Catalyzed Reduction of 4-Nitro- phenol (4-NP). Applied Surface Science, 255, 3989-3993.
[35] Liu, M., Guo, B., Zou, Q., Du, M. and Jia, D. (2008) Interactions between Halloysite Nanotubes and 2,5-Bis(2-benzo- xazolyl) Thiophene and Their Effects on Reinforcement of Polypropylene/Halloysite Nanocomposites. Nanotechnology, 19, Article ID: 205709.
[36] Giri, S., Trewyn, B.G., Stellmaker, M.P. and Lin, V.S.Y. (2005) Stimuli-Responsive Controlled-Release Delivery System Based on Mesoporous Silica Nanorods Capped with Magnetic Nanoparticles. Angewandte Chemie International Edition, 44, 5038-5044.
[37] Cavallaro, G., Lazzara, G., Milioto, S., Palmisano, G. and Parisi, F. (2014) Halloysite Nanotube with Fluorinated Lumen: Non-Foaming Nanocontainer for Storage and Controlled Release of Oxygen in Aqueous Media. Journal of Colloid and Interface Science, 417, 66-71.
[38] Cirkva, V., Polák, R., Paleta, O., Kefurt, K., Moravcová, J., Kodicek, M. and Forman, S. (2004) Novel Perfluoroalkylated Derivatives of D-Galactopyranose and Xylitol for Biomedical Uses. Hemocompatibility and Effect on Perfluorocarbon Emulsions. Carbohydrate Research, 339, 2177-2185.
[39] Abdullayev, E., Joshi, A., Wei, W., Zhao, Y. and Lvov, Y. (2012) Enlargement of Halloysite Clay Nanotube Lumen by Selective Etching of Aluminum Oxide. ACS Nano, 6, 7216-7226.
[40] Borgis, D. and Vuilleumier, R. (2000) Transport and Infrared Spectroscopy of the Hydrated Proton. Abstracts of Papers of the American Chemical Society, 220, U191-U191.
[41] Afanasiev, A. and Minogin, V. (2010) van der Waals Interaction of an Atom with the Internal Surface of a Hollow Submicrometer-Size Cylinder. Physical Review A, 82, Article ID: 052903.
[42] Tjatjopoulos, G.J., Feke, D.L. and Mann, J.A. (1988) Molecule-Micropore Interaction Potentials. The Journal of Physical Chemistry, 92, 4006-4007.
[43] Pujar, N.S. and Zydney, A.L. (1997) Charge Regulation and Electrostatic Interactions for a Spherical Particle in a Cylindrical Pore. Journal of Colloid and Interface Science, 192, 338-349.
[44] Bowen, W.R., Filippov, A.N., Sharif, A.O. and Starov, V.M. (1999) A Model of the Interaction between a Charged Particle and a Pore in a Charged Membrane Surface. Advances in Colloid and Interface Science, 81, 35-72.
[45] Jones, J.E. (1924) On the Determination of Molecular Fields. II. From the Equation of State of a Gas. Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, 106, 463-477.
[46] Zhang, L. and Winkler, P. (2006) Debye-Hückel Screening and Fluctuations. Chemical Physics, 329, 338-342.
[47] Russel, W.B., Saville, D.A. and Schowalter, W.R. (1989) Colloidal Dispersions. Journal of Fluid Mechanics, 222, 692- 694.
[48] Chapman, S. and Cowling, T.G. (1991) The Mathematical Theory of Non-Uniform Gases. Cambridge University Press, Cambridge.
[49] Waugh, A. and Grant, A., Eds. (2007) Anatomy and Physiology in Health and Illness. 10th Edition, Churchill Livingstone Elsevier, London.
[50] Wenbo, W. (2013) Halloysite Nanotube Composites for Sustained Release of Antimocrobial Agents (Antiseptics and Antibiotics. PhD Thesis, Louisiana Tech University, Ruston. (Retrieved from ProQuest Dissertations and Theses, Accession Order No. AAT 3580371)
[51] Bordeepong, S., Bhongsuwan, D., Pungrassami, T. and Bhongsuwan, T. (2011) Characterization of Halloysite from Thung Yai District, Nakhon Si Thammarat Province, in Southern Thailand. Songklanakarin Journal of Science & Technology, 33, 599-607.
[52] Patterson, S.H. and Murray, H.H. (1984) Kaolin, Refractory Clay, Ball Clay, and Halloysite in North America, Hawaii, and the Caribbean Region. US Department of the Interior, Geological Survey, For Sale by the Distribution Branch, USGS, Alexandria.
[53] Theng, B.K.G., Russell, M., Churchman, G.J. and Parfitt, R.L. (1982) Surface Properties of Allophane, Halloysite, Imogolite. Clays and Clay Minerals, 30, 143-149.
[54] Kaufhold, S., Kaufhold, A., Jahn, R., Brito, S., Dohrmann, R., Hoffmann, R., et al. (2009) A New Massive Deposit of Allophane Raw Material in Ecuador. Clays and Clay Minerals, 57, 72-81.
[55] Nagarajan, R., Ed. (2012) Nanomaterials for Biomedicine. Vol. 1119, American Chemical Society.
[56] Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P. and Peppas, N.A. (1983) Mechanisms of Solute Release from Porous Hydrophilic Polymers. International Journal of Pharmaceutics, 15, 25-35.
[57] Phaechamud, T., Koizumi, T. and Ritthidej, G.C. (2000) Chitosan Citrate as Film Former: Compatibility with Water- Soluble Anionic Dyes and Drug Dissolution from Coated Tablet. International Journal of Pharmaceutics, 198, 97-111.
[58] Joshi, A., Montes, C., Salehi, S., Allouche, E. and Lvov, Y. (2014) Optimization of Geopolymer Properties by Coating of Fly-Ash Microparticles with Nanoclays. Journal of Inorganic and Organometallic Polymers and Materials, 25, 1- 11.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.