Peptide‐Decorated Liposomes Enhance Fungal Targeting and Antifungal Drug Delivery

Abstract Candida infections are a clinical challenge due to a limited repertoire of antifungal drugs, biofilm development, and antifungal drug resistance. Fungi‐targeted liposomes can improve antifungal drug solubility and delivery while reducing toxicity by enhancing fungal cell interaction. Here, liposomes that encapsulate the antifungal drug, posaconazole (POS), are decorated with the peptide, penetratin (Pen). Liposome‐fungal cell interaction increases significantly from ∼50% to >80% upon Pen conjugation with both C. albicans and C. auris . Pen‐decorated liposomes containing POS inhibit planktonic C. albicans and C. auris at liposome concentrations up to 8× lower than non‐Pen‐decorated liposomes, suggesting enhanced POS delivery due to increased fungal targeting. Furthermore, Pen‐decorated liposomes inhibit C. albicans and C. auris biofilm formation at POS concentrations that are up to 1300× lower than free POS. Finally, Pen‐decorated liposomes exhibit promising prophylactic activity in an intradermal C. albicans murine infection model, reducing fungal burden by ∼60% compared to non‐targeting POS‐loaded liposomes. Overall, Pen‐decorated, POS‐loaded liposomes expand the antifungal drug repertoire against Candida spp. and serve as a platform technology to improve the treatment of fungal infections.