Silver Carboxylate-Eluting Titanium Dioxide/Polydimethyl Siloxane Antibiotic-Independent Antimicrobial Coating as a Safe and Efficacious Alternative for Antibiotic Resistance

羧酸银洗脱二氧化钛/聚二甲基硅氧烷不依赖抗生素的抗菌涂层作为抗生素耐药性的安全有效替代品

• 批准号: 10374141
• 负责人: Dioscaris Garcia
• 金额: $ 8.2万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-17 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374141
• 关键词: Acne; Address; Adherence; Analysis of Variance; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Apoptosis; Atmosphere; Bacteria; Bacterial Infections; Biological Assay; Biological Availability; Bypass; Carbon Dioxide; Cell Line; Cell Survival; Cell Wall; Cells; Chemistry; Clinical; Colistin; Confidence Intervals; Data; Development; Dose; Endothelium; Enterococcus faecalis; Environment; Evaluation; Exposure to; Formulation; Future; Goals; Grant; Healthcare; Hospitals; Hour; Human; Humidifier; Implant; Incubated; Infection; Laboratories; Linezolid; Membrane; Metabolic; Microbial Biofilms; Molecular; Multi-Drug Resistance; Multiple Bacterial Drug Resistance; Muscle Fibers; Musculoskeletal; Necrosis; Nosocomial Infections; Osteoblasts; Patient-Focused Outcomes; Patients; Penetrance; Penetration; Pharmacology; Prevention; Property; Prosthesis; Race; Radial; Reporting; Research; Research Personnel; Resistance; Resort; Safety; Siloxanes; Silver; Silver Nitrate; Societies; Spinal; Sulfadiazine; Surgical Wound Infection; Surgical sutures; Technology; Testing; Therapeutic; Therapeutic Index; Time; Tobramycin; Toxic effect; Triton X100; United States; United States National Institutes of Health; Vancomycin; Vancomycin resistant enterococcus; antimicrobial; base; carboxylate; cell type; combat; cost; cytotoxic; cytotoxicity; disability; dosage; drug resistant pathogen; experimental study; implantable device; improved; innovation; keratinocyte; logarithm; methicillin resistant Staphylococcus aureus; multidrug-resistant Pseudomonas aeruginosa; multimodality; nanoparticle; new technology; novel; pathogen; pathogenic bacteria; pathogenic fungus; prevent; resistant strain; response; success; titanium dioxide; wound healing

Project Summary Introduction: Antibiotic resistance has forced clinicians and researchers into a race to find antimicrobial alternative strategies to improve patient outcomes. Surgical site infections (SSIs) are particularly difficult due to treat and prevent due to the exposure to the non-sterile external environment. To address current antimicrobial needs, we propose to evaluate a novel and pharmacologically-predictable antimicrobial technology composed of a silver carboxylate eluting matrix of titanium dioxide (TiO2) and polydimethyl siloxane (PDMS). This antimicrobial formulation utilizes the multi-modal antimicrobial properties of silver to treat bacterial infections regardless of antibiotic resistance, without the toxicity of previous formulations. We hypothesize silver carboxylate will be efficacious against drug-resistant pathogens with no local toxicity to primary cell types involved in wound healing. Significance: The extensive use of implantable devices has accentuated the need for new technologies as periprosthetic infections cost billions of dollars to healthcare and significant patient disability. The rise in antibiotic resistance and lack of novel antibiotics create a significant worldwide problem. In contrast to the single mechanism of antibiotic action, silver has multiple antimicrobial mechanisms that are difficult for bacteria to counteract, thus limiting potential for resistance and providing a viable alternative to resistant strains. Innovation: The proposed chemistry shows improved penetration into the cell wall of bacteria, while controlling rate of release and bioavailability via the customizable TiO2/PDMS matrix. We hypothesize this new chemistry will decrease toxicity associated with unpredictable concentrations and prolonged presence of clinically used broad spectrum and “last resort” antibiotics. Previous research on this technology has focused on prevention of bacterial adherence on spinal implants, prosthetic liners, and sutures. Over a dozen bacterial and fungal pathogens have been tested with considerable levels of antimicrobial activities from 24 to 72 hours. Research Plan: We propose 2 specific aims which will: 1) Provide Evidence of Silver Carboxylate’s Low Cytotoxicity in Primary Cell Lines Involved in Wound Healing using the cell metabolic activity assay MTT, LDH, Necrosis and Apoptosis. 2) Quantify Silver Carboxylate’s Potency against Commonly-Encountered Antibiotic-Resistant Pathogen via dose-response curves and Kirby Bauer Assays. Proposed aims will provide additional data on the efficacy of the chemistry against bacteria regardless of gram designation or antimicrobial resistance while showing low toxicity against cells involved in wound healing. This data will be utilized to pursue an R01 grant which will focus on determining the mechanism of action of silver carboxylate, penetrance into biofilms, as well as activity against biofilm persister cells.

项目总结

项目成果

Silver carboxylate-TiO2/polydimethyl siloxane is a safe and effective antimicrobial with significant wound care potential.

羧酸银-TiO2/聚二甲基硅氧烷是一种安全有效的抗菌剂，具有显着的伤口护理潜力。

• DOI: 10.1097/oi9.0000000000000299
• 发表时间: 2024
• 期刊: OTA international : the open access journal of orthopaedic trauma
• 作者: Allu,Sai;Whitaker,Colin;Stone,Benjamin;Vishwanath,Neel;Clippert,Drew;Jouffroy,Elia;Antoci,Valentin;Born,Christopher;Garcia,DioscarisR
• 通讯作者: Garcia,DioscarisR

Silver Carboxylate as an Antibiotic-Independent Antimicrobial: A Review of Current Formulations, in vitro Efficacy, and Clinical Relevance.

• DOI: 10.18103/mra.v10i12.3388
• 发表时间: 2022-12
• 期刊: Medical research archives
• 作者: Mette, Makena;Connolly, William;Vishwanath, Neel;Allu, Sai;Whitaker, Colin;Stone, Benjamin K;Antoci, Valentin;Born, Christopher T;Garcia, Dioscaris R
• 通讯作者: Garcia, Dioscaris R