Transdermal drug delivery is of vital importance for medical treatments. However, user adherence to long-term repetitive drug delivery poses a grand challenge. Furthermore, the dynamic and unpredictable disease progression demands a pharmaceutical treatment that can be actively controlled in real-time to ensure medical precision and personalization. Here, we report a spatiotemporal on-demand patch (SOP) that integrates drug-loaded microneedles with biocompatible metallic membranes to enable electrically triggered active control of drug release. Precise control of drug release to targeted locations (<1 mm2), rapid drug release response to electrical triggers (<30 s), and multi-modal operation involving both drug release and electrical stimulation highlight the novelty. Solution-based fabrication ensures high customizability and scalability to tailor the SOP for various pharmaceutical needs. The wireless-powered and digital-controlled SOP demonstrates great promise in achieving full automation of drug delivery, improving user adherence while ensuring medical precision. Based on these characteristics, we utilized SOPs in sleep studies. We revealed that programmed release of exogenous melatonin from SOPs improve sleep of mice, indicating potential values for basic research and clinical treatments.
Transdermal drug delivery provides convenient and pain-free self-administration for personalized therapy. However, challenges remain in treating acute diseases mainly due to their inability to timely administrate therapeutics and precisely regulate pharmacokinetics within a short time window. Here we report the development of active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management. Through the integration of active acoustic metamaterials, a compact therapeutic patch is integrated for penetration of skin stratum corneum and active percutaneous transport of therapeutics with precise control of dose and rate over time. Moreover, the patch device quantitatively regulates the dosage and release kinetics of therapeutics and achieves better delivery performance in vivo than through subcutaneous injection. As a proof-of-concept application, we show our method can reverse life-threatening acute allergic reactions in a female mouse model of anaphylaxis via a multi-burst delivery of epinephrine, showing better efficacy than a fixed dosage injection of epinephrine, which is the current gold standard ‘self-injectable epinephrine’ strategy. This innovative method may provide a promising means to manage acute disease for personalized medicine.
more » « less- NSF-PAR ID:
- 10397414
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 14
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Transdermal delivery is an attractive delivery method that increases bioavailability, is suitable for a wide variety of therapeutics, and offers stable delivery outcomes. However, many therapeutics are unable to readily cross the stratum corneum. Microneedles mechanically disrupt the cutaneous barrier to deliver small molecules, proteins, and vaccines. To date, microneedles have not been used in conjunction with coacervate, a liquid–liquid phase separation that protects unstable proteins. A three‐layer microneedle for the controlled release of three different molecules is designed. Through micromolding, microneedles are efficiently generated, which benefits product scalability. The microneedles have good mechanical integrity and effectively penetrate porcine skin ex vivo. The three layers, in the microneedles, release the cargo in a three‐phase manner. The released protein maintains its structure well. Moreover, layer thickness can be controlled by varying fabrication parameters. The microneedles can incorporate both small molecule drugs and protein therapeutics, thus promising uses in multi‐drug therapies through a single treatment.
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