A breakthrough in transdermal drug delivery was reported in a recent study published in Nature Communications.
Scientists have developed an electrically activated patch with biocompatible metal membranes and microneedles, allowing for precise, repeated, personalized, and safe drug delivery.
Study: Digitale Automatisierung der transdermalen Arzneimittelabgabe mit hoher räumlich-zeitlicher Auflösung. Bildnachweis: Andrey_Popov/Shutterstock.com
While transdermal drug delivery through injection needles is a faster, cost-effective, safe, and relatively painless process for administering pharmaceutical products like vaccines and biopharmaceuticals, this method continues to pose significant challenges for chronic diseases requiring long-term and repeated treatments, especially in terms of patient compliance.
Injection needles also raise concerns about safe disposal and the risk of bloodborne pathogen transmission, apart from requiring trained personnel for widespread use.
Recently explored strategies for transdermal drug delivery include sonophoresis or the use of ultrasound for drug delivery through the skin; iontophoresis, in which weak electric currents are used for transdermal drug delivery, heat, electroporation, microneedles, and photomechanical waves.
While some of these methods have significantly improved certain aspects of drug delivery, such as user-friendliness and painless drug delivery, a method of transdermal drug delivery suitable for chronic diseases requiring coordinated and precise drug delivery over extended periods is not in sight for clinical application.
About the Study
In the present study, researchers used electrical external triggers in combination with a biocompatible metal membrane capable of carrying drug-laden microneedles to develop the transdermal drug delivery patch, known as spatiotemporal on-demand patch (SOP).
Microneedles were tested and used for various applications, such as administering nanocomposites, peptides, nucleic acids, small molecules, and other types of drugs.
Furthermore, the chemical functionality of microneedles can be modulated by altering their structural integrity, leading to a variety of release profiles.
Microneedles with a core-shell structure containing a drug reservoir can be pre-programmed to release the drug at the right time by adjusting the degradability of the core-shell. These microneedles can also load multiple drugs to allow for stepwise drug delivery during combined therapy.
However, complex fabrication methods present a challenge to the scalability of such methods, and pre-programmed microneedles cannot be altered after use.
On the other hand, microneedles can be programmed through chemical functionalization to release biopharmaceuticals through self-regulation and self-perception.
For example, materials such as aminoimidazole and phenylboronic acid have been used to manufacture microneedles that react to body glucose and undergo structural changes to release insulin.
External triggers such as electrical impulses have also been utilized to control the active delivery of drugs. When combined with health monitors, this technology results in a closed-loop therapy system.
The integration of biocompatible metal gates made from thin metal membranes has improved the active control of drug delivery using microneedles.
Magnesium, molybdenum, and gold are some of the metals used to form these gates, and the use of electrical impulses to trigger the corrosive or oxidative opening of these gates can be used to actively release the drugs as needed.
According to the results, the SOP was made from approximately 150 nanometers thick gold layer applied to the microneedles to encapsulate and protect the drugs during the standby phase.
Furthermore, electrical impulses were used to trigger these controlled microneedles to release the drugs as needed, making the SOP highly controllable spatially and temporally.
The gold coating of these sealed microneedles can be dissolved by applying a direct current of approximately 2.5 volts for 30 seconds, initiating drug delivery.
In addition, a wireless communication method integrated into the SOP through microfabrication using low-energy Bluetooth and near-field communication also enables the activation of individual microneedles or sections of the patch for drug release.
Moreover, each microneedle provides spatial control of less than one square millimeter, allowing for ultrafine spatial-temporal control in combination with a 30-second drug release time.
In vivo experiments in mouse models also showed that using SOP to release exogenous melatonin resulted in improved sleep, highlighting the potential of SOP for clinical treatments and neurological research in animal models.
Furthermore, successful intracranial SOP implantation experiments in mice suggested its suitability for the sequential administration of drugs to specific brain regions for treating neurological disorders.
In conclusion, the study reported the development of a transdermal drug delivery system that combines biocompatible, metal-controlled microneedles with wireless communication and electrical triggering systems to deliver drugs precisely and actively through the skin.
The fully automated aspect of the system aims to improve treatment adherence.
Wang, Y., Chen, Z., Davis, B., Lipman, W., Xing, S., Zhang, L., Wang, T., Hafiz, P., Xie, W., Yan, Z., Huang, Z., Song, J. & Bai, W. (2024). Digitale Automatisierung der transdermalen Arzneimittelabgabe mit hoher räumlich-zeitlicher Auflösung. Naturkommunikation15(1), 511. doi: https://doi.org/10.1038/s41467023445320