Living Bacteria in Thermoresponsive Gel for Treating Fungal Infections

Lufton, Maayan; Bustan, Or; Eylon, Bat‐hen; Shtifman-Segal, Ella; Croitoru-Sadger, Tsuf; Shagan, Alona; Shabtay-Orbach, Ayelet; Corem-Salkmon, Enav; Berman, Judith; Nyska, Abraham; Mizrahi, Boaz

doi:10.1002/adfm.201801581

Cited by 43 publications

(45 citation statements)

References 41 publications

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“…Consequently, rational selection of pharmacologically acceptable carriers is very important when formulating HDPs-related therapeutics, which will determine the eventual therapeutic performance. According to the results of activity testing as well as in vitro characterization of degradation, drug release, and antimicrobial kinetics, the optimal carrier favoring ND delivery among tested hydrogels was finally determined to be the Plu hydrogel which has already been applied in the controlled delivery of diverse agents, such as small molecules 45 , genes 33 , and even bacteria 46 , due to its thermosensitive nature and in situ assembly behaviors as well as excellent biocompatibility.…”

Section: Discussionmentioning

confidence: 99%

Nanodefensin-encased hydrogel with dual bactericidal and pro-regenerative functions for advanced wound therapy

Luo¹,

Sun²,

Zhang³

et al. 2021

Theranostics

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Background: Host defense peptides (HDPs) have emerged as a novel therapeutic paradigm for wound management; however, their clinical applications remain a challenge owing to their poor pharmacological properties and lack of suitable pharmaceutical formulations. Nanodefensin (ND), a nanoengineered human α-defensin 5 (HD5), has shown improved pharmacological properties relative to the parent compound. In this study, we engineered a nanodefensin-encased hydrogel (NDEFgel), investigated the effects of NDEFgel on wound healing, and elucidated underlying mechanisms. Method: ND was chemically synthesized and tested functions by in vitro antimicrobial and scratch assays and western blotting. Different NDEFgels were evaluated by in vitro characterizations including degradation, drug release and antimicrobial activity. In full-thickness excisional murine models, the optimal NDEFgel was directly applied onto wound sites, and the efficacy was assessed. Moreover, the underlying mechanisms of pro-regenerative effect developed by NDEFgel were also explored. Results: Apart from bactericidal effects, ND modulated fibroblast behaviors by promoting migration and differentiation. Among the tested hydrogels, the Pluronic F127 (Plu) hydrogel represented the most desirable carrier for ND delivery owing to its favorable controlled release and compatibility with ND. Local treatment of NDEFgel on the wound bed resulted in accelerated wound regeneration and attenuated bacterial burden. We further demonstrated that NDEFgel therapy significantly upregulated genes related to collagen deposition and fibroblasts, and increased the expression of myofibroblasts and Rac1. We therefore found that Rac1 is a critical factor in the ND-induced modulation of fibroblast behaviors in vitro through a Rac1-dependent cytoskeletal rearrangement. Conclusion: Our results indicate that NDEFgel may be a promising dual-action therapeutic option for advanced wound management in the future.

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Section: Discussionmentioning

confidence: 99%

Nanodefensin-encased hydrogel with dual bactericidal and pro-regenerative functions for advanced wound therapy

Luo¹,

Sun²,

Zhang³

et al. 2021

Theranostics

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“…DDW was used as a control. We noted that the tested hydrogels can penetrate and absorbed through the skin (Lufton et al 2018; Yurdasiper, Ertan, and Heard 2018; Rancan 2016). Therefore, each hydrogel was administrated daily and the treated area was remained uncovered for the entire period of the experiment.…”

Section: Methodsmentioning

confidence: 99%

Local Toxicity of Topically Administrated Thermoresponsive Systems: In Vitro Studies with In Vivo Correlation

et al. 2018

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Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.

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“…Rapid emergence of multidrug‐resistant bacteria affects public health adversely and is a major concern that needs effective solutions . We have thus included some of the latest examples where hydrogels are used in treating microbial infections.…”

Section: Hydrogels For Medical Applicationsmentioning

confidence: 99%

“…Lufton et al describe the administration of live bacteria incorporated in a thermoresponsive hydrogel, which hardens once introduced on the skin and continuously delivers antifungal agents . Here, gram positive bacteria Bacillus subtilis is incorporated into a thermoresponsive hydrogel made of the polymer Pluronic F‐127 ((Poly (ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide)), which has a LCST close to the body temperature and can harden at room temperature.…”

Section: Hydrogels For Medical Applicationsmentioning

confidence: 99%

Hydrogels for Medical and Environmental Applications

2020

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Hydrogels are heavily‐hydrated 3D microliths having loose, porous structures. Unlike organogels, elastomers, and carbohydrates, hydrogels are structures with water as a continuous phase/solvent. Being water‐based, they provide a lot of scope for facile improvizations in their structure and in introducing chemical functionalities. They can house various functional materials in their highly porous networks, making them potential candidates for diverse applications. Various possibilities in using different starting materials for hydrogels are described herein, and it is shown how choosing and optimizing these components that make up the hydrogel can modify their properties. Studying hydrogels and their formulations will enable the understanding of their multifunctional properties. External stimuli‐responsive and functional systems can be designed out of these microliths to suit a wide range of applications like biosensing, cancer therapy, regenerative medicine, drug delivery, environmental parameter sensing, water desalination, heavy‐metal adsorption, and water treatment. Environmental degradation is occurring at an alarming rate, cascading the adverse effects on the environment but also causing detrimental effects in public health. In this review, multiple perspectives from state‐of‐the‐art literature are brought together to examine hydrogels as very powerful, sustainable, cost‐effective, and simple solutions for the betterment of the environment and subsequently, public health.

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Living Bacteria in Thermoresponsive Gel for Treating Fungal Infections

Cited by 43 publications

References 41 publications

Nanodefensin-encased hydrogel with dual bactericidal and pro-regenerative functions for advanced wound therapy

Nanodefensin-encased hydrogel with dual bactericidal and pro-regenerative functions for advanced wound therapy

Local Toxicity of Topically Administrated Thermoresponsive Systems: In Vitro Studies with In Vivo Correlation

Hydrogels for Medical and Environmental Applications

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