Antifungal hydrogels

Zumbuehl, Andréas; Ferreira, Lino; Kuhn, Duncan M.; Astashkina, Anna; Long, Lisa; Yeo, Yoon; Iaconis, Tiffany; Ghannoum, Mahmoud A.; Fink, Gerald R.; Langer, Robert; Kohane, Daniel S.

doi:10.1073/pnas.0705250104

Cited by 106 publications

(70 citation statements)

References 26 publications

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“…Nevertheless, 1 M simvastatin is still ϳ30-fold higher than the plasma level achieved after standard oral dosing in humans (28). Although pharmacoepidemiologic studies have found no increased risk for fetal anomalies in pregnant women taking statins (45), reformulating simvastatin as a coating for catheter lumens may be a more feasible approach, as has been done with other substances such as EDTA or amphotericin, where oral dosage is impractical (46,47).…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Inhibits Candida albicans Biofilm In Vitro

et al. 2009

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By inhibiting the conversion of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) to mevalonate, statins impair cholesterol metabolism in humans. We reasoned that statins might similarly interfere with the biosynthesis of ergosterol, the major sterol of the yeast cell membrane. As assessed by spectrophotometric and microscopic analysis, significant inhibition of biofilm production was noted after 16-h incubation with 1, 2.5, and 5 M simvastatin, concentrations that did not affect growth, adhesion, or hyphal formation by C. albicans in vitro. Higher concentrations (10, 20, and 25 M simvastatin) inhibited biofilm by Ͼ90% but also impaired growth. Addition of exogenous ergosterol (90 M) overcame the effects of 1 and 2.5 M simvastatin, suggesting that at least one mechanism of inhibition is interference with ergosterol biosynthesis. Clinical isolates from blood, skin, and mucosal surfaces produced biofilms; biofilms from bloodstream isolates were similarly inhibited by simvastatin. In the absence of fungicidal activity, simvastatin's interruption of a critical step in an essential metabolic pathway, highly conserved from yeast to man, has unexpected effects on biofilm production by a eukaryotic pathogen. (Pediatr Res 66: 600-604, 2009)

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Section: Discussionmentioning

confidence: 99%

Simvastatin Inhibits Candida albicans Biofilm In Vitro

et al. 2009

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“…Our group developed a rabbit model of catheter-associated C. albicans biofilm infection ( 41 ) and showed that 7 days postinfection, quantitative catheter cultures consistently yielded >2 log CFU/catheter segment, which is considered the threshold for catheter-related infections. We also used a subcutaneous mouse model to evaluate the effect of coating a catheter substrate with amphogels (amphotericin B–based gel) on Candida biofilms ( 42 ) and demonstrated that the subcutaneous model has utility in studies evaluating catheter surface modification on the ability of Candida to form biofilms.…”

Section: Experimental Models Of Candida Biofilmsmentioning

confidence: 99%

Candida Biofilms: Development, Architecture, and Resistance

2015

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Intravascular device–related infections are often associated with biofilms (microbial communities encased within a polysaccharide-rich extracellular matrix) formed by pathogens on the surfaces of these devices. Candida species are the most common fungi isolated from catheter-, denture-, and voice prosthesis–associated infections and also are commonly isolated from contact lens–related infections (e.g., fungal keratitis). These biofilms exhibit decreased susceptibility to most antimicrobial agents, which contributes to the persistence of infection. Recent technological advances have facilitated the development of novel approaches to investigate the formation of biofilms and identify specific markers for biofilms. These studies have provided extensive knowledge of the effect of different variables, including growth time, nutrients, and physiological conditions, on biofilm formation, morphology, and architecture. In this article, we will focus on fungal biofilms (mainly Candida biofilms) and provide an update on the development, architecture, and resistance mechanisms of biofilms.

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“…A number of strategies such as polymeric and peptide hydrogels, nanoparticles, microemulsion, liposomes, niosomes, or ethosomes that can function as drug depots for delivering the antifungals at the site of infections have been reported. [15][16][17][18][19][20] However, these formulations need to be applied frequently to maintain sustained release of the drugs. 21 Nonwoven fiber mats produced by electrospinning have the potential for a wide range of applications such as filters, composites, drug carriers, wound dressing, and tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

Lakshminarayanan

Sridhar

Loh

et al. 2014

IJN

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Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections.

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Antifungal hydrogels

Cited by 106 publications

References 26 publications

Simvastatin Inhibits Candida albicans Biofilm In Vitro

Simvastatin Inhibits Candida albicans Biofilm In Vitro

Candida Biofilms: Development, Architecture, and Resistance

Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

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