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Breaking Biofilm Barriers: Using CATH-ICG-Loaded Bilayer Dissolving Microneedle-Assisted Photodynamic Therapy for
Yaseen Hussain1, Amos Dormocara1, Huifang Li1
1College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Molecular Pharmaceutics
|May 27, 2025
Summary
Novel dissolving microneedles loaded with Cathelicidin (CATH) and indocyanine green, combined with photodynamic therapy, effectively treat deep skin fungal infections by disrupting biofilms and enhancing drug penetration.
Area of Science:
- Dermatology
- Mycology
- Nanotechnology
- Drug Delivery
Background:
- Deep skin fungal infections, especially those caused by biofilm-forming *Candida albicans*, are challenging due to antifungal resistance.
- The stratum corneum limits the penetration of conventional antifungal treatments.
- Antimicrobial peptides like Cathelicidin (CATH) show antifungal activity but struggle with biofilm penetration.
Purpose of the Study:
- To develop and evaluate a transdermal delivery system using CATH-loaded dissolving microneedles (DMNs) combined with photodynamic therapy (PDT) for deep dermal *C. albicans* biofilm infections.
- To overcome the limitations of CATH's penetration into fungal biofilms.
- To enhance the efficacy of antifungal therapy against resistant fungal infections.
Main Methods:
- Fabrication of dissolving microneedles (DMNs) loaded with Cathelicidin (CATH) and indocyanine green (ICG).
- Application of photodynamic therapy (PDT) using near-infrared (NIR) irradiation on CATH-ICG-DMNs.
- Evaluation of efficacy using in vitro, ex vivo, and in vivo models of *C. albicans* biofilm infections.
- Mechanistic validation using qRT-PCR and propidium iodide staining.
Main Results:
- CATH-ICG-DMNs with NIR irradiation achieved a significant reduction (approximately 94%) in fungal burden.
- Photodynamic therapy disrupted the fungal biofilm matrix, facilitating deeper CATH penetration.
- A synergistic effect between CATH and PDT was observed, enhancing antifungal activity.
- Mechanistic studies confirmed the proposed hypothesis for biofilm disruption and enhanced efficacy.
Conclusions:
- The developed microneedle-based PDT strategy is a promising approach for treating deep skin fungal infections.
- This method effectively overcomes biofilm-mediated resistance to antifungal agents.
- The study highlights the potential of combining novel antimicrobial peptides with advanced drug delivery systems for enhanced therapeutic outcomes.
