Hostname: page-component-848d4c4894-5nwft Total loading time: 0 Render date: 2024-06-11T00:00:12.747Z Has data issue: false hasContentIssue false
  • English
  • Français

Halloysite Nanotube Vehicles for Drug Delivery Through a Model Blood–Brain Barrier

Published online by Cambridge University Press:  01 January 2024

M. Saleh ,
N. Prajapati ,
A. Karan ,
N. Rahman ,
A. Stavitskaya ,
M. DeCoster  and
Y. Lvov Open the ORCID record for Y. Lvov [Opens in a new window]
M. Saleh
Affiliation:
Institute for Micromanufacturing and Biomedical Engineering Program, Louisiana Tech University, Ruston, LA 71270, USA
N. Prajapati
Affiliation:
Institute for Micromanufacturing and Biomedical Engineering Program, Louisiana Tech University, Ruston, LA 71270, USA
A. Karan
Affiliation:
Institute for Micromanufacturing and Biomedical Engineering Program, Louisiana Tech University, Ruston, LA 71270, USA
N. Rahman
Affiliation:
Institute for Micromanufacturing and Biomedical Engineering Program, Louisiana Tech University, Ruston, LA 71270, USA
A. Stavitskaya
Affiliation:
Gubkin Russian State University, Moscow 119991, Russia
M. DeCoster
Affiliation:
Institute for Micromanufacturing and Biomedical Engineering Program, Louisiana Tech University, Ruston, LA 71270, USA
Y. Lvov*
Affiliation:
Institute for Micromanufacturing and Biomedical Engineering Program, Louisiana Tech University, Ruston, LA 71270, USA
*
*E-mail address of corresponding author: ylvov@latech.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Epilepsy treatment requires anti-seizure medical formulations; available medications have various painful side effects and penetrate the brain–blood barrier poorly. A promising method is the use of natural clay nanocontainers for drug delivery through this membrane barrier. Halloysites (Hly) are biocompatible, 50-nm diameter tubes with a positively charged, hollow inner lumen and negatively charged outer shell and are available naturally. These characteristics enable them to be versatile as drug loaded ‘nano-torpedoes’ effectively penetrating cell membranes. The endothelial cells are a major cell type in the blood–brain barrier that provides for the selective permeability separating the circulating blood and allowing only the passage of glucose, water, and amino acids, but not traditional drug formulations. Nanotubes encapsulating rhodamine isothiocyanate and ionomycin penetration through the rat-brain microvascular endothelial cells followed by a prolonged 24-h drug release was demonstrated. A model membrane was set up across 0.4-μm-pore polystyrene transwell supports covered by seeding endothelial and astrocyte cells to mimic the blood–brain barrier in vivo. This barrier demonstrated a dual permeation mechanism (inter-cell accumulation and through-passing) for loaded Hlys, exploiting the potential of this nanoclay in the trans-membrane delivery of drugs. Use of Hly nanotubes as drug carriers to penetrate the brain microvascular endothelial barrier and to deliver the payload displayed a new approach for the treatment of brain diseases such as epilepsy.

Keywords

Blood–brain barrierDrug deliveryHalloysiteNano-torpedo
Type
Article
Information
Clays and Clay Minerals , Volume 69 , Issue 5: Clay Minerals in Health Applications , October 2021 , pp. 603 - 611
Copyright
Copyright © The Clay Minerals Society 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

This paper belongs to a special issue on ‘Clay Minerals in Health Applications’

References

Artursson, P. (1991). Cell cultures as models for drug absorption across the intestinal mucosa. Critical Reviews in Therapeutic Drug Carrier Systems, 8(4), 305–330.Google ScholarPubMed
Artursson, P., Palm, K., & Luthman, K. (2001). Caco-2 monolayers in experimental and theoretical predictions of drug transport. Advanced Drug Delivery Reviews, 46(1–3), 27–43. 10.1016/S0169-409X(00)00128-9 (The article was published originally in Advanced Drug Delivery Reviews, 22, (1996), 67–84.)CrossRefGoogle ScholarPubMed
Bennewitz, M. F., & Saltzman, W. M. (2009). Nanotechnology for delivery of drugs to the brain for epilepsy. Neurotherapeutics, 6(2), 323–336. https://doi.org/10.1016/j.nurt.2009.01.018CrossRefGoogle Scholar
Bozdağ Pehlivan, S. (2013). Nanotechnology-based drug delivery systems for targeting imaging and diagnosis of neurodegenerative diseases. Pharmaceutical Research, 30(10), 2499–2511. https://doi.org/10.1007/s11095-013-1156-7CrossRefGoogle Scholar
Dzamukova, M., Naumenko, E., Badrutdinov, A., Lvov, Y., & Fakhrullin, R. (2015a). Enzyme-activated intracellular drug delivery with tubule clay nanoformulation. Scientific Reports, 5, 10560. https://doi.org/10.1038/srep10560CrossRefGoogle Scholar
Dzamukova, M., Naumenko, E., Rozhina, E., Trifonov, A., & Fakhrullin, R. (2015b). Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters. Nano Research, 8, 2515–2532. https://doi.org/10.1007/s12274-015-0759-1CrossRefGoogle Scholar
Fakhrullina, G., Khakimova, E., Akhatova, F., Lazzara, G., Parisi, F., & Fakhrullin, R. (2019). Selective antimicrobial effects of curcumin @ halloysite nanoformulation: A Caenorhabditis elegans study. ACS Applied Materials and Interfaces, 11, 23050–23064. https://doi.org/10.1021/acsami.9b07499CrossRefGoogle ScholarPubMed
Hu, Y., Chen, J., Li, X., Sun, Y., Huang, S., Li, Y., Liu, H., Xu, J., & Zhong, S. (2017). Multifunctional halloysite nanotubes for targeted delivery and controlled release of doxorubicin in-vitro and in-vivo studies viability tests and microscopy study. Nanotechnology, 28, 375101. https://doi.org/10.1088/1361-6528/aa8393CrossRefGoogle Scholar
Hubatsch, I., Ragnarsson, E., & Artursson, P. (2007). Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nature Protocols, 2, 2111–2119. https://doi.org/10.1038/nprot.2007.303CrossRefGoogle ScholarPubMed
Kamalieva, R., Ishmukhametov, I., Batasheva, S., Rozhina, E., & Fakhrullin, R. (2018). Uptake of halloysite clay nanotubes by human cells: Colourimetric. Nano Structure Nano Objects, 15, 54–60. https://doi.org/10.1016/j.nanoso.2018.03.009CrossRefGoogle Scholar
Kruchkova, M., Danilushkina, A., Lvov, Y., & Fakhrullin, R. (2016). In vivo toxicity study of nanoclays and graphene oxide with Paramecium caudatum. Environmental Science: Nano, 3, 442–452. https://doi.org/10.1039/c5en00201jGoogle Scholar
Lazzara, G., Cavallaro, G., Panchal, A., Fakhrullin, R., Stavitskaya, A., Vinokurov, V., & Lvov, Y. (2018). An assembly of organic-inorganic composites using halloysite clay nanotubes. Current Opinion in Colloid & Interface Science, 35, 42–50. https://doi.org/10.1016/j.cocis.2018.01.002CrossRefGoogle Scholar
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. https://doi.org/10.1016/j.progpolymsci.2014.04.004CrossRefGoogle Scholar
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. https://doi.org/10.1002/adma.201502341CrossRefGoogle ScholarPubMed
Mahringer, A., Ott, M., & Fricker, G. (2013). The blood–brain barrier: An introduction to its structure and function. The Blood–Brain Barrier, pp. 1–20. Springer, Berlin, https://doi.org/10.1007/7355_2013_20Google Scholar
Mehdia, Y., Fizira, M., Itatahinea, A., Hea, H., & Dramoua, P. (2018). Preparation of multifunctional PEG-graft-halloysite nanotubes for controlled drug release, Tumor cell targeting, and bio-imaging. Colloidal Surfaces B Biointerface., 170, 322–329. https://doi.org/10.1016/j.colsurfb.2018.06.042Google Scholar
Prajapati, N., & DeCoster, M. (2020). Nitric oxide modulation and calcium dysregulation in brain endothelial and astrocyte cell co-cultures during inflammation. Biomedical Sciences Instrumentation, 56, 24–27.Google Scholar
Prajapati, N., Karan, A., Khezerlou, E., & DeCoster, M. A. (2021). The immunomodulatory potential of copper and silver based self-assembled metal organic biohybrids nanomaterials in cancer theranostics. Frontiers in Chemistry, 8, 1296. https://doi.org/10.3389/fchem.2020.629835CrossRefGoogle ScholarPubMed
Rodrigues, J. P., Prajapati, N., DeCoster, M. A., Poh, S., & Murray, T. A. (2021). Efficient LRP1-mediated uptake and low cytotoxicity of peptide L57 in vitro shows its promise as CNS drug delivery vector. Journal of Pharmaceutical Sciences, 110(2), 824–832. https://doi.org/10.1016/j.xphs.2020.09.019CrossRefGoogle ScholarPubMed
Saleh, M. Y., Prajapati, N., DeCoster, M. A., & Lvov, Y. (2020). Tagged halloysite nanotubes as a carrier for intercellular delivery in brain microvascular endothelium. Frontiers in Bioengineering and Biotechnology, 8, 451. https://doi.org/10.3389/fbioe.2020.00451CrossRefGoogle ScholarPubMed
Santos, A. C., Pereira, I., Reis, S., Veiga, F., Saleh, M., & Lvov, Y. (2019). Biomedical potential of clay nanotube formulations and their toxicity assessment. Expert Opinion on Drug Delivery, 16(11), 1169–1182. https://doi.org/10.1080/17425247.2019.1665020CrossRefGoogle ScholarPubMed
Silva, G. A. (2008). Nanotechnology approaches to crossing the bloodbrain barrier and drug delivery to the CNS. BMC Neuroscience, 9(Suppl 3), S4. https://doi.org/10.1186/1471-2202-9-S3-S4CrossRefGoogle ScholarPubMed
Stenberg, P., Norinder, U., Luthman, K., & Artursson, P. (2001). Experimental and computational screening models for the prediction of intestinal drug absorption. Journal of Medicinal Chemistry, 44(12), 1927–1937. https://doi.org/10.1021/jm001101aCrossRefGoogle ScholarPubMed
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. https://doi.org/10.1021/bm9014446CrossRefGoogle Scholar
Vivès, E., Brodin, P., & Lebleu, B. (1997). A truncated HIV-1 tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. Journal of Biological Chemistry, 272(25), 16010–16017. https://doi.org/10.1074/jbc.272.25.16010CrossRefGoogle ScholarPubMed
Vivès, E., Schmidt, J., & Pèlegrin, A. (2008). Cell-penetrating and cell-targeting peptides in drug delivery. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1786(2), 126–138. https://doi.org/10.1016/j.bbcan.2008.03.001CrossRefGoogle ScholarPubMed
Wang, X., Gong, J., Gui, Z., Hu, T., & Xu, X. (2018). Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of mice after 30-day repeated oral administration. Environmental Toxicology, 33(6), 623–630. https://doi.org/10.1002/tox.22543CrossRefGoogle ScholarPubMed
World Health Organization. (2020). Epilepsy. www.who.int/newsroom/fact-sheets/detail/epilepsy. Accessed July 2021Google Scholar
Yang, J., Wu, Y., Shen, Y., Zhou, C., Li, Y.-F., He, R.-R., & Liu, M. (2016). Enhanced therapeutic efficacy of doxorubicin for breast cancer using chitosan oligosaccharide-modified halloysite nanotubes. ACS Applied Materials and Interfaces, 8, 26578–26590. https://doi.org/10.1021/acsami.6b09074CrossRefGoogle ScholarPubMed
Zhang, Z., Luo, X., Wu, Y.-P., Wu, F., Li, Y.-F., He, R.-R., & Liu, M. (2019). Rod in tube: A novel nanoplatform for highly effective chemo-photothermal combination therapy toward breast cancer. ACS Applied Materials and Interfaces, 11, 3690–3703. https://doi.org/10.1021/acsami.8b17533CrossRefGoogle Scholar
Zhao, X., Wan, Q., Fu, X., Meng, X., Ou, X., Zhong, R., Zhou, Q., & Liu, M. (2019). Toxicity evaluation of one-dimensional nanoparticles using Caenorhabditis elegans: a comparative study of halloysite nanotubes and chitin nanocrystals. ACS Sustained Chemical Engineering, 7, 18965–18975.CrossRefGoogle Scholar