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Electrospun patches to deliver combination drug therapy for fungal infections
Karolina Dziemidowicz1, Mark Meszarik1, Jacopo Piovesan1
1Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, United Kingdom.
Abstract:
Fungal infections, though affecting healthcare globally, receive insufficient attention in clinical and academic settings. Invasive fungal infections, particularly caused by combat wounds, have been identified as a critical threat by the US Department of Defense. Monotherapy with traditional antifungals is often insufficient, and so combination therapies are explored to enhance treatment efficacy. However, systemic combination treatments can result in severe adverse effects, suggesting the need for localised delivery systems, such as drug-loaded electrospun patches, to administer antifungals directly to the infection site. This proof-of-concept study hypothesised that dual amorolfine and terbinafine therapy slowly releasing from electrospun patches would be an effective way of eradicating Candida albicans when the patch was applied directly to the fungal colony. The feasibility of creating electrospun materials loaded with amorolfine and terbinafine for combination antifungal therapy was investigated. Electrospinning was used to fabricate polycaprolactone (PCL) patches with varying drug loadings (2.5%, 5%, and 10% w/w) of amorolfine and terbinafine either individually or in combination. The incorporation of both drugs in the fibres was confirmed, with the drugs predominantly in an amorphous state. Results showed that combination therapy patches had a significantly greater and prolonged antifungal effect compared to monotherapy patches, with larger zones of inhibition and sustained efficacy over at least 7 days. This study therefore demonstrates that PCL-based electrospun patches containing amorolfine and terbinafine provide superior antifungal activity against C. albicans compared to monotherapy patches. This approach could lower required drug doses, reducing adverse effects, and enhance patient compliance due to prolonged drug release, leading to more effective antifungal therapy.
Insights
Dual antifungal therapy with amorolfine and terbinafine in electrospun patches offers enhanced efficacy against Candida albicans. This localized drug delivery system provides sustained release, improving treatment outcomes for fungal infections.
Area of Science:
- Biomaterials Science
- Pharmaceutical Sciences
- Mycology
Background:
- Fungal infections pose a global health challenge, with invasive forms, especially from combat wounds, being a critical concern.
- Traditional antifungal monotherapy is often inadequate, and systemic combination therapies can lead to severe adverse effects.
- Localized drug delivery systems are needed to improve antifungal treatment efficacy and reduce systemic toxicity.
Purpose of the Study:
- To investigate the feasibility of creating electrospun polycaprolactone (PCL) patches loaded with amorolfine and terbinafine for combination antifungal therapy.
- To evaluate the efficacy of dual amorolfine and terbinafine therapy delivered via electrospun patches against Candida albicans.
- To assess the sustained drug release and antifungal activity of the combination therapy patches.
Main Methods:
- Fabrication of polycaprolactone (PCL) electrospun patches with varying drug loadings (2.5%, 5%, 10% w/w) of amorolfine and terbinafine.
- Confirmation of drug incorporation and state within the electrospun fibers using analytical techniques.
- In vitro assessment of antifungal activity, including zones of inhibition and sustained efficacy over time against Candida albicans.
Main Results:
- Electrospun PCL patches successfully incorporated both amorolfine and terbinafine, with drugs primarily in an amorphous state.
- Combination therapy patches demonstrated significantly greater and prolonged antifungal effects compared to monotherapy patches.
- Sustained antifungal efficacy was observed for at least 7 days with the combination patches.
Conclusions:
- PCL-based electrospun patches loaded with amorolfine and terbinafine provide superior antifungal activity against Candida albicans compared to monotherapy.
- This localized delivery approach has the potential to reduce required drug doses and minimize adverse effects.
- The enhanced efficacy and prolonged drug release offer a promising strategy for more effective antifungal therapy and improved patient compliance.
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