Nanoparticle System Improves Delivery of Antifungal Drug

Engineers at Brown University have designed a nanoscale drug delivery system that enhances the effectiveness of an antifungal drug against Candida species, including drug-resistant strains such as Candida auris. Their findings, published in Advanced Functional Materials, describe how the researchers used liposomes—a form of lipid-based nanoparticle—to deliver the antifungal compound posaconazole directly to fungal cells using a peptide-guided targeting approach.

Liposomes are spherical carriers made from fat-like substances. They can encapsulate medications and improve their delivery to targeted cells. In this study, the team improved the specificity of liposomes for fungal pathogens by attaching a short peptide sequence known to bind fungal cells to the surface of the liposomes. This modification increased the drug's ability to reach and affect fungal cells, including those protected within biofilms.

Biofilms are dense microbial communities that adhere to surfaces and are notably resistant to antifungal treatments. The targeted liposomes were effective at much lower drug concentrations compared to the free drug alone, inhibiting fungal growth and biofilm formation in laboratory assays.

The researchers tested several peptides and identified one called penetratin as the most effective. They incorporated this peptide onto liposomes loaded with posaconazole, a drug approved by the US Food and Drug Administration to prevent fungal overgrowth in immunocompromised patients. In lab-based experiments, these peptide-decorated liposomes were more likely to attach to Candida cells than standard liposomes, confirming the targeting mechanism worked as intended.

In comparative tests, the targeted liposomes inhibited fungal growth at concentrations up to eight times lower than those required for free posaconazole and prevented biofilm formation at doses up to 1,300 times lower. The researchers also tested the formulation on human cells derived from tissues commonly affected by fungal infections. The treated cells showed no toxicity, indicating the approach may be safe for further development.

To evaluate therapeutic potential in a living organism, the team used a mouse model of skin infection caused by Candida albicans. Mice treated with the targeted liposomes showed a 60% reduction in fungal burden compared to those treated with conventional liposomes, suggesting that this targeted approach could significantly enhance treatment outcomes.

The team is now planning to extend their work to evaluate how well this delivery system performs with drugs used to treat active infections, rather than just those used for prevention.

Reference: LaMastro V, Walker D, Liu J, et al. Peptide-decorated liposomes enhance fungal targeting and antifungal drug delivery. Adv Fun Mat. 2025. doi: 10.1002/adfm.202508570

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