Hydrogel degradation triggered by pH for the smart release of antibiotics to combat bacterial infection

Lu, Zhentan; Zhang, Jiaqi; Yu, Zhenliang; Liu, Qiongzhen; Liu, Ke; Li, Mufang; Wang, Dong

doi:10.1039/c6nj03260e

Cited by 29 publications

(22 citation statements)

References 25 publications

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“…Bacterial infection leads to the pH fluctuation because of the complex process of healing, immune responses and bacterial metabolism. The pH has been found to fall to the value as low as 5.5 at the infection sites due to low-oxygen fermentation, triggering the production of lactic acid and acetic acid 5–7 . In addition, the production of hydrogen peroxide (H 2 O 2 ) in the infecting wounds is the first response of the immune system during inflammation to exert antimicrobial activity 8,9 .…”

Section: Introductionmentioning

confidence: 99%

Intelligent Metal-Phenolic Metallogels as Dressings for Infected Wounds

Anh

Huang

2019

Sci Rep

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In this study, we report a metallogel developed based on metal-phenolic coordination of natural low-cost polyphenolic molecule and metal ions. Gelation occurs by mixing tannic acid (TA) and group (IV) titanium ions (Ti IV ) to form TA-Ti IV gel. The TA-Ti IV gel exhibits good capability to incorporate diverse metal ions by in situ co-gelation. Herein, five antimicrobial metal ions, i.e. ferric (Fe III ), copper (Cu II ), zinc (Zn II ), cobalt (Co II ) and nickel (Ni II ) ions, were employed to include in TA-Ti IV gels for developing intelligent dressings for infected wounds. The chemical and coordinative structures of TA-Ti IV metallogels were characterized by UV-Vis and Fourier-transform infrared (FT-IR) spectroscopies. Cytotoxicity of antimicrobial metallogels was explored by MTT assay with NIH 3T3 fibroblasts. The release of metal ions was evaluated by inductively coupled plasma mass spectrometry (ICP-MS), indicating the different releasing profiles upon the coordinative interactions of metal ions with TA. The formation and disassembly of metallogels are sensitive to the presence of acid and an oxidizer, H 2 O 2 , which are substances spontaneously generated in infected wounds due to the metabolic activity of bacteria and the intrinsic immune response. The Cu II releasing rates of TA-Ti IV -Cu II metallogels at different pH values of 5.5, 7.4 and 8.5 have been studied. In addition, addition of H 2 O 2 trigger fast release of Cu II as a result of oxidation of galloyl groups in TA. Consequently, the antimicrobial potency of TA-Ti IV -Cu II metallogels can be simultaneously activated while the wounds are infected and healing. The antimicrobial property of metallogels against Gram-negative Escherichia coli , and Gram-positive Methicillin-Resistant Staphylococcus aureus (USA300) and Staphylococcus epidermidis has been investigated by agar diffusion test. In an animal model, the TA-Ti IV -Cu II metallogels were applied as dressings for infected wounds, indicating faster recovery in the wound area and extremely lower amount of bacteria around the wounds, compared to TA-Ti IV gels and gauze. Accordingly, the intelligent nature derived metallogels is a promising and potential materials for medical applications.

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Section: Introductionmentioning

confidence: 99%

Intelligent Metal-Phenolic Metallogels as Dressings for Infected Wounds

Anh

Huang

2019

Sci Rep

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“…pH-sensitive hydrogels Hydrogels are water-swollen biomaterials which can be made to expand or contract in response to various stimuli. 39 As such, they are promising "smart materials" for use in chemically responsive drug delivery, 40,41 artificial muscles, 42 and chemical sensors using cantilevers, 43,44 photonic band gaps, 45 magneotelastic, 46 or electrical readout. 45,46 For a pHsensing implantable device, a biocompatible polymer material is required with sensitivity within the physiologic range of pH about 4 -7.5 to facilitate usage in vivo.…”

Section: Resultsmentioning

confidence: 99%

Implanted chemical sensors for functional radiography

Arifuzzaman¹,

Millhouse²,

Raval³

et al. 2017

Preprint

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A biomedical sensor is designed to noninvasively measure local pH changes on the surface of implanted devices for detecting and monitoring implant-associated infection using plain radiography. The sensor comprises a radiopaque pin embedded within a polyacrylic acid-based hydrogel. pH-modulated hydrogel expansion and contraction is determined by radiographically measuring the pin position. The sensor was calibrated in a series of standard pH buffers, and tested in a bacterial growth culture. The sensor calibration was insensitive to changes in temperature and ionic strength within the normal physiological range. The response time depended on sensor thickness, and was approximately 30 min for 1 mm thick films. Radiographic measurements were also performed through tissue and bone with the sensor attached to an orthopedic plate fixated to a human cadaver tibia. Plain radiographs were selected for readout since X-rays are routinely used in inpatient and outpatient settings for structural or anatomical information. The chemically-responsive hydrogel sensors can provide additional functional information in a clinical setting by indicating local chemical concentrations near the implant surface using routinely obtained radiographs.

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“…In a broader antimicrobial context, pH-responsive hydrogels may well be used as controlled-release systems to treat a range of different infections. Lu and colleagues [51], designed a pH-sensitive poly(acrylic acid) (PAA) and p -(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) composite hydrogel. The hydrogel decomposed gradually when placed in a weak acidic microenvironment, but was stable under normal physiological and weakly basic environments.…”

Section: Endogenous Stimuli-responsive Antibiotic Drug-delivery Symentioning

confidence: 99%

Recent Developments in Antibacterial Therapy: Focus on Stimuli-Responsive Drug-Delivery Systems and Therapeutic Nanoparticles

et al. 2019

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Conventional drugs used for antibacterial therapy display several limitations. This is not due to antibiotics being ineffective, but rather due to their low bioavailability, limited penetration to sites of infection and the rise of drug-resistant bacteria. Although new delivery systems (e.g., nanoparticles) that are loaded with antibacterial drugs have been designed to overcome these limitations, therapeutic efficacy does not seem to have improved. Against this backdrop, stimuli-responsive antibiotic-loaded nanoparticles and materials with antimicrobial properties (nanoantibiotics) present the ability to enhance therapeutic efficacy, while also reducing drug resistance and side effects. These stimuli can either be exogenous (e.g., light, ultrasound) or endogenous (e.g., pH, variation in redox gradient, enzymes). This promising therapeutic approach relies on advances in materials science and increased knowledge of microorganism growth and biofilm formation. This review provides an overview in the field of antibacterial drug-delivery systems and nanoantibiotics that benefit from a response to specific triggers, and also presents a number of future prospects.

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Hydrogel degradation triggered by pH for the smart release of antibiotics to combat bacterial infection

Abstract: pH-Triggered smart drug release for the treatment of bacterial infection.

Cited by 29 publications

References 25 publications

Intelligent Metal-Phenolic Metallogels as Dressings for Infected Wounds

Intelligent Metal-Phenolic Metallogels as Dressings for Infected Wounds

Implanted chemical sensors for functional radiography

Recent Developments in Antibacterial Therapy: Focus on Stimuli-Responsive Drug-Delivery Systems and Therapeutic Nanoparticles

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