Hyaluronic Acid-Based CuS Nanoenzyme Biodegradable Microneedles for Treating Deep Cutaneous Fungal Infection without Drug Resistance
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Bingjie Wang1, Wenshang Zhang1, Qi Pan2
1Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Abstract:
Deep cutaneous fungal infection (DCFI) is difficult to be treated by the traditional topical application due to low drug transdermal efficiency, poor fungicidal effect, and easy to develop drug resistance. Here, we report a novel biodegradable microneedle patch (CuS/PAF-26 MN) for DCFI treatment. CuS/PAF-26 MN is composed of hyaluronic acid (HA) and sodium carboxymethylcellulose (CMC-Na), which can simultaneously deliver copper sulfide nanoenzyme (CuS NE) and antimicrobial peptide (PAF-26). CuS NE catalyzes hydrogen peroxide to produce reactive oxygen species (ROS), and PAF-26 directly destroys the cell membrane of fungi. The combination of ROS toxicity produced by CuS NE and the destruction of fungal membrane by PAF-26 shows strong antifungal activities without drug resistance. The antifungal effect of CuS/PAF-26 MN is significantly superior to that of traditional ointment, CuS MN or PAF-26 MN in a DCFI mouse model. Therefore, CuS/PAF-26 MN shows a promising application prospect for treating DCFI.
Insights
A novel microneedle patch effectively treats deep cutaneous fungal infections (DCFI). This patch delivers copper sulfide nanoenzyme and an antimicrobial peptide, offering a potent, resistance-free antifungal treatment superior to traditional methods.
Area of Science:
- Biomaterials Science
- Dermatology
- Nanotechnology
Background:
- Deep cutaneous fungal infections (DCFI) present treatment challenges due to poor topical drug delivery and emerging resistance.
- Conventional treatments often suffer from low efficacy and the development of drug resistance.
Purpose of the Study:
- To develop and evaluate a novel biodegradable microneedle patch (CuS/PAF-26 MN) for enhanced DCFI treatment.
- To assess the synergistic antifungal effects of simultaneously delivered copper sulfide nanoenzyme (CuS NE) and antimicrobial peptide (PAF-26).
Main Methods:
- Fabrication of a microneedle patch using hyaluronic acid (HA) and sodium carboxymethylcellulose (CMC-Na).
- Incorporation of CuS NE and PAF-26 into the microneedle patch for co-delivery.
- Evaluation of antifungal efficacy in a DCFI mouse model, comparing CuS/PAF-26 MN to conventional treatments.
Main Results:
- CuS NE generates reactive oxygen species (ROS), while PAF-26 disrupts fungal cell membranes, leading to potent synergistic antifungal activity.
- The combined approach demonstrated significant antifungal effects, overcoming drug resistance.
- CuS/PAF-26 MN showed superior efficacy compared to traditional ointments, CuS MN, and PAF-26 MN in the DCFI mouse model.
Conclusions:
- The developed CuS/PAF-26 MN represents a promising new strategy for treating DCFI.
- This microneedle patch offers enhanced drug transdermal efficiency and overcomes limitations of traditional topical antifungal therapies.
- The synergistic action of CuS NE and PAF-26 provides a potent and resistance-free treatment option for deep cutaneous fungal infections.
