Issue 17, 2023

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

Abstract

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.

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

  • This article is part of the themed collection: Microneedles

Supplementary files

Article information

Article type
Paper
Submitted
07 Jun 2023
Accepted
08 Jul 2023
First published
17 Jul 2023
This article is Open Access
Creative Commons BY-NC license

Biomater. Sci., 2023,11, 5846-5858

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

K. V. Tobin and N. K. Brogden, Biomater. Sci., 2023, 11, 5846 DOI: 10.1039/D3BM00972F

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements