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Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice

The blood–brain barrier (BBB) is an obstacle to the permeation of most therapeutic drugs into the brain, limiting treatments for neurological disorders. Drugs loaded within nanocarriers that pass through the BBB can overcome this limitation. Halloysite consists of naturally occurring biocompatible c...

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Autores principales: Yanamadala, Yaswanthi, Saleh, Mahdi Y., Williams, Afrika A., Lvov, Yuri, Murray, Teresa A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253593/
https://www.ncbi.nlm.nih.gov/pubmed/37298599
http://dx.doi.org/10.3390/ijms24119648
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author Yanamadala, Yaswanthi
Saleh, Mahdi Y.
Williams, Afrika A.
Lvov, Yuri
Murray, Teresa A.
author_facet Yanamadala, Yaswanthi
Saleh, Mahdi Y.
Williams, Afrika A.
Lvov, Yuri
Murray, Teresa A.
author_sort Yanamadala, Yaswanthi
collection PubMed
description The blood–brain barrier (BBB) is an obstacle to the permeation of most therapeutic drugs into the brain, limiting treatments for neurological disorders. Drugs loaded within nanocarriers that pass through the BBB can overcome this limitation. Halloysite consists of naturally occurring biocompatible clay nanotubes of 50 nm diameter and 15 nm lumen, allowing the loading and sustained release of loaded drugs. These have demonstrated the ability to transport loaded molecules into cells and organs. We propose to use halloysite nanotubes as a “nano-torpedo” for drug delivery through the BBB due to their needle-like shape. To determine if they can cross the BBB using a non-invasive, clinically translatable route of administration, we loaded halloysite with either diazepam or xylazine and delivered these intranasally to mice daily over six days. The sedative effects of these drugs were observed in vestibulomotor tests conducted at two, five, and seven days after the initial administration. Behavioral tests were conducted 3.5 h after administration to show that the effects were from halloysite/delivered drugs and not from the drug alone. As expected, the treated mice performed more poorly than the sham, drug alone, and halloysite-vehicle-treated mice. These results confirm that halloysite permeates the BBB to deliver drugs when administered intranasally.
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spelling pubmed-102535932023-06-10 Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice Yanamadala, Yaswanthi Saleh, Mahdi Y. Williams, Afrika A. Lvov, Yuri Murray, Teresa A. Int J Mol Sci Article The blood–brain barrier (BBB) is an obstacle to the permeation of most therapeutic drugs into the brain, limiting treatments for neurological disorders. Drugs loaded within nanocarriers that pass through the BBB can overcome this limitation. Halloysite consists of naturally occurring biocompatible clay nanotubes of 50 nm diameter and 15 nm lumen, allowing the loading and sustained release of loaded drugs. These have demonstrated the ability to transport loaded molecules into cells and organs. We propose to use halloysite nanotubes as a “nano-torpedo” for drug delivery through the BBB due to their needle-like shape. To determine if they can cross the BBB using a non-invasive, clinically translatable route of administration, we loaded halloysite with either diazepam or xylazine and delivered these intranasally to mice daily over six days. The sedative effects of these drugs were observed in vestibulomotor tests conducted at two, five, and seven days after the initial administration. Behavioral tests were conducted 3.5 h after administration to show that the effects were from halloysite/delivered drugs and not from the drug alone. As expected, the treated mice performed more poorly than the sham, drug alone, and halloysite-vehicle-treated mice. These results confirm that halloysite permeates the BBB to deliver drugs when administered intranasally. MDPI 2023-06-02 /pmc/articles/PMC10253593/ /pubmed/37298599 http://dx.doi.org/10.3390/ijms24119648 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yanamadala, Yaswanthi
Saleh, Mahdi Y.
Williams, Afrika A.
Lvov, Yuri
Murray, Teresa A.
Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice
title Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice
title_full Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice
title_fullStr Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice
title_full_unstemmed Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice
title_short Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice
title_sort clay nanotubes loaded with diazepam or xylazine permeate the brain through intranasal administration in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253593/
https://www.ncbi.nlm.nih.gov/pubmed/37298599
http://dx.doi.org/10.3390/ijms24119648
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