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Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency

Naltrexone (NTX) can be transdermally delivered using microneedles (MN) to treat opioid and alcohol misuse disorders, but delivery is blunted by rapid in vivo micropore closure. Poloxamer (P407), a thermosensitive biocompatible hydrogel, sustains NTX delivery through MN-treated skin by generating a...

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Autores principales: Tobin, Kevin V., Brogden, Nicole K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443048/
https://www.ncbi.nlm.nih.gov/pubmed/37455601
http://dx.doi.org/10.1039/d3bm00972f
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author Tobin, Kevin V.
Brogden, Nicole K.
author_facet Tobin, Kevin V.
Brogden, Nicole K.
author_sort Tobin, Kevin V.
collection PubMed
description Naltrexone (NTX) can be transdermally delivered using microneedles (MN) to treat opioid and alcohol misuse disorders, but delivery is blunted by rapid in vivo micropore closure. Poloxamer (P407), a thermosensitive biocompatible hydrogel, sustains NTX delivery through MN-treated skin by generating a drug depot within the micropores. Optimizing P407 formulations could maintain sustained delivery after micropore closure while reducing required patch sizes, which would be more discreet and preferred by most patients. Here we developed NTX-loaded P407 gels with chemical permeation enhancers (CPEs) and used these novel formulations alongside MN treatment to enhance NTX permeation, utilizing parallel micropore and intact skin transport pathways. We analyzed physicochemical and rheological properties of CPE-loaded P407 formulations and selected formulations with DMSO and benzyl alcohol for further study. In vitro permeation tests demonstrated more consistent and sustained NTX delivery through MN-treated porcine skin from 16% P407 formulations vs. aqueous solutions. P407 with 1% benzyl alcohol and 10% DMSO significantly, P < 0.05, increased flux through MN-treated skin vs. formulations with benzyl alcohol alone. This formulation would require a smaller size patch than previously used to deliver NTX in humans, with half the NTX concentration. This is the first time poloxamer biomaterials have been used in combination with CPEs to improve MN-assisted transdermal delivery of an opioid antagonist. Here we have demonstrated that P407 in combination with CPEs effectively sustains NTX delivery in MN-treated skin while requiring less NTX than previously needed to meet clinical goals.
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spelling pubmed-104430482023-08-23 Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency Tobin, Kevin V. Brogden, Nicole K. Biomater Sci Chemistry Naltrexone (NTX) can be transdermally delivered using microneedles (MN) to treat opioid and alcohol misuse disorders, but delivery is blunted by rapid in vivo micropore closure. Poloxamer (P407), a thermosensitive biocompatible hydrogel, sustains NTX delivery through MN-treated skin by generating a drug depot within the micropores. Optimizing P407 formulations could maintain sustained delivery after micropore closure while reducing required patch sizes, which would be more discreet and preferred by most patients. Here we developed NTX-loaded P407 gels with chemical permeation enhancers (CPEs) and used these novel formulations alongside MN treatment to enhance NTX permeation, utilizing parallel micropore and intact skin transport pathways. We analyzed physicochemical and rheological properties of CPE-loaded P407 formulations and selected formulations with DMSO and benzyl alcohol for further study. In vitro permeation tests demonstrated more consistent and sustained NTX delivery through MN-treated porcine skin from 16% P407 formulations vs. aqueous solutions. P407 with 1% benzyl alcohol and 10% DMSO significantly, P < 0.05, increased flux through MN-treated skin vs. formulations with benzyl alcohol alone. This formulation would require a smaller size patch than previously used to deliver NTX in humans, with half the NTX concentration. This is the first time poloxamer biomaterials have been used in combination with CPEs to improve MN-assisted transdermal delivery of an opioid antagonist. Here we have demonstrated that P407 in combination with CPEs effectively sustains NTX delivery in MN-treated skin while requiring less NTX than previously needed to meet clinical goals. The Royal Society of Chemistry 2023-07-17 /pmc/articles/PMC10443048/ /pubmed/37455601 http://dx.doi.org/10.1039/d3bm00972f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Tobin, Kevin V.
Brogden, Nicole K.
Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency
title Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency
title_full Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency
title_fullStr Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency
title_full_unstemmed Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency
title_short Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency
title_sort thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443048/
https://www.ncbi.nlm.nih.gov/pubmed/37455601
http://dx.doi.org/10.1039/d3bm00972f
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