Abstract
Purpose
Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are debilitating conditions resulting from a progressive degeneration of nerve cells that is attributed to oxidative stress. Given the role of hydrogen sulphide (H2S), an endogenously produced signalling molecule involved in regulating of oxidative stress, exogenous administration of H2S has been proposed as a potential treatment strategy. This research study involved an investigation into the mechanical properties of microneedles loaded AP39 (a H2S donor), their ability to penetrate skin and effectiveness to deliver AP39 across murine skin. Additionally, the study explored the capability of permeated AP39 to release H2S and thus quench H2O2-induced oxidative stress in neuroblastoma cells, SHSY5Y cells.
Methods
Microneedles were prepared using 20% w/v polyvinyl alcohol (PVA) of either 27,000 or 67,000 molecular weights, with or without trehalose 15% w/v. Mechanical and insertion properties of microneedles were determined and optimised formulation applied to murine skin to observe AP39 flux through the skin. Collected media was applied to a microvasculature blood–brain-barrier model to evidence AP39 permeation, following which, permeated AP39 was applied to an oxidative stress scenario in SHSY5Y cells to assess AP39 potential in limiting oxidative stress.
Results
Microneedle fracture testing observed the microneedles produced from polyvinyl alcohol 67,000 with trehalose were best able to withstand compression force applied. Microneedles formulated from PVA 67,000 were best able to penetrate the parafilm model. Further, the PVA 67,000 with trehalose microneedle formulation was observed to pierce murine skin and deliver 32.84 ± 2.11% of applied AP39 across the skin over 32 h. AP39 transport across the HUVEC microvasculature model gave an apparent membrane permeability of 18.6 ± 1.4. Finally, AP39 attenuated H2O2-induced oxidative stress as well as inflammation in SHSY5Y cells; resulting in reduced neurodegeneration burden.
Conclusion
These findings demonstrate that microneedle patches for the transdermal delivery of AP39 may provide a promising clinical approach in the treatment of neurological disorder associated with oxidative stress.
Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are debilitating conditions resulting from a progressive degeneration of nerve cells that is attributed to oxidative stress. Given the role of hydrogen sulphide (H2S), an endogenously produced signalling molecule involved in regulating of oxidative stress, exogenous administration of H2S has been proposed as a potential treatment strategy. This research study involved an investigation into the mechanical properties of microneedles loaded AP39 (a H2S donor), their ability to penetrate skin and effectiveness to deliver AP39 across murine skin. Additionally, the study explored the capability of permeated AP39 to release H2S and thus quench H2O2-induced oxidative stress in neuroblastoma cells, SHSY5Y cells.
Methods
Microneedles were prepared using 20% w/v polyvinyl alcohol (PVA) of either 27,000 or 67,000 molecular weights, with or without trehalose 15% w/v. Mechanical and insertion properties of microneedles were determined and optimised formulation applied to murine skin to observe AP39 flux through the skin. Collected media was applied to a microvasculature blood–brain-barrier model to evidence AP39 permeation, following which, permeated AP39 was applied to an oxidative stress scenario in SHSY5Y cells to assess AP39 potential in limiting oxidative stress.
Results
Microneedle fracture testing observed the microneedles produced from polyvinyl alcohol 67,000 with trehalose were best able to withstand compression force applied. Microneedles formulated from PVA 67,000 were best able to penetrate the parafilm model. Further, the PVA 67,000 with trehalose microneedle formulation was observed to pierce murine skin and deliver 32.84 ± 2.11% of applied AP39 across the skin over 32 h. AP39 transport across the HUVEC microvasculature model gave an apparent membrane permeability of 18.6 ± 1.4. Finally, AP39 attenuated H2O2-induced oxidative stress as well as inflammation in SHSY5Y cells; resulting in reduced neurodegeneration burden.
Conclusion
These findings demonstrate that microneedle patches for the transdermal delivery of AP39 may provide a promising clinical approach in the treatment of neurological disorder associated with oxidative stress.
| Original language | English |
|---|---|
| Number of pages | 14 |
| Journal | Journal of Pharmaceutical Investigation |
| DOIs | |
| Publication status | Published - 22 Nov 2024 |
Bibliographical note
Copyright © The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.Keywords
- Controlled-release
- Microneedles
- Neurodegeneration
- Oxidative stress
- Transdermal drug delivery