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Dec, 2024;13 (30): e2401157.

Fungal Enzyme-Responsive Hydrogel Drug Delivery Platform for Triggered Antifungal Release.

Noel Vera-González, Carly Deusenbery, Veronica LaMastro, Anita Shukla
Author Information
  1. Noel Vera-González: School Of Engineering, Institute for Biology, Engineering, and Medicine, Brown University, 184 Hope Street, Providence, RI, 02912, USA.
  2. Carly Deusenbery: School Of Engineering, Institute for Biology, Engineering, and Medicine, Brown University, 184 Hope Street, Providence, RI, 02912, USA. ORCID
  3. Veronica LaMastro: School Of Engineering, Institute for Biology, Engineering, and Medicine, Brown University, 184 Hope Street, Providence, RI, 02912, USA. ORCID
  4. Anita Shukla: School Of Engineering, Institute for Biology, Engineering, and Medicine, Brown University, 184 Hope Street, Providence, RI, 02912, USA. ORCID
PMID: 39210641 DOI: 10.1002/adhm.202401157

Abstract

Fungal infections can lead to debilitating consequences if they are not treated effectively. Antifungal drugs used to treat these infections can be toxic and overuse contributes to growing antifungal resistance. Candida spp., particularly C. albicans, are implicated in a majority of these infections. Virulent C. albicans produce secreted aspartic proteases (Saps) that aid in pathogen tissue invasion and proliferation at an infected site. Here, fungi-responsive hydrogels are developed that degrade in the presence of Saps to provide a triggered release of encapsulated liposomal antifungals. The hydrogel backbone incorporates a Sap-cleavable peptide sequence enabling Sap-responsive degradation. Hydrogels are found to effectively degrade in the presence of Saps extracted from C. albicans. Encapsulated liposomal antifungals show similar release kinetics as hydrogel degradation products in the presence of Saps, supporting a degradation-dependent release mechanism. Antifungal liposome-loaded responsive hydrogels exhibit successful eradication of C. albicans cultures and remain stable in sterile murine wound fluid. Finally, no significant cytotoxicity is observed for murine fibroblast cells and red blood cells exposed to hydrogel degradation products. These fungi-responsive hydrogels have the potential to be used for local, on-demand delivery of antifungal drugs, for effective treatment of fungal infections while helping to limit unnecessary exposure to these therapeutics.

Keywords

Candida albicans antifungal biomaterials enzyme‐responsive drug delivery hydrogels

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Grants

  1. N000141712651/Office of Naval Research
  2. N000142012455/Office of Naval Research
  3. 1644760/National Science Foundation
  4. 1942418/National Science Foundation

MeSH Term

Antifungal Agents
Hydrogels
Candida albicans
Animals
Mice
Drug Delivery Systems
Liposomes
Aspartic Acid Proteases
Candidiasis

Chemicals

Antifungal Agents
Hydrogels
Liposomes
Aspartic Acid Proteases
Journal Article

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