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Injectable in situ cross-linking hydrogels for local antifungal therapy

Paper ID Volume ID Publish Year Pages File Format Full-Text
9850 648 2010 9 PDF Available
Title
Injectable in situ cross-linking hydrogels for local antifungal therapy
Abstract

Invasive fungal infections can be devastating, particularly in immunocompromised patients, and difficult to treat with systemic drugs. Furthermore, systemic administration of those medications can have severe side effects. We have developed an injectable local antifungal treatment for direct administration into existing or potential sites of fungal infection. Amphotericin B (AmB), a hydrophobic, potent, and broad-spectrum antifungal agent, was rendered water-soluble by conjugation to a dextran-aldehyde polymer. The dextran-aldehyde–AmB conjugate retained antifungal efficacy against Candida albicans. Mixing carboxymethylcellulose-hydrazide with dextran-aldehyde formed a gel that cross-linked in situ by formation of hydrazone bonds. The gel provided in vitro release of antifungal activity for 11 days, and contact with the gel killed Candida for three weeks. There was no apparent tissue toxicity in the murine peritoneum and the gel caused no adhesions. Gels produced by entrapment of a suspension of AmB in CMC–dextran without conjugation of drug to polymers did not release fungicidal activity, but did kill on contact. Injectable systems of these types, containing soluble or insoluble drug formulations, could be useful for treatment of local antifungal infections, with or without concurrent systemic therapy.

Keywords
Controlled drug release; Hydrogel; Cellulose; Dextran; Biocompatibility
First Page Preview
Injectable in situ cross-linking hydrogels for local antifungal therapy
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 6, February 2010, Pages 1444–1452
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering