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氨基查尔酮功能化的粘膜粘附水凝胶在钛表面及蜡螟模型中的抗菌和抗生物膜活性:体外和体内研究

Antimicrobial and anti-biofilm activity of a mucoadhesive hydrogel functionalized with aminochalcone on titanium surfaces and in Galleria mellonella model: In vitro and in vivo study.

作者信息

Ribeiro Lima Francisco Ricardo, Figueiredo Luciene Cristina de, Oliveira Braga Arthur Rodrigues, Garcia Mayara Aparecida Rocha, Carvalho Suzana Gonçalves, Regasini Luís Octávio, Chorilli Marlus, Sardi Janaina de Cássia Orlandi

机构信息

Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, São Paulo, Brazil.

Department of Chemistry and Environmental Sciences, Júlio de Mesquita Filho University, São Jose Do Rio Preto, Brazil.

出版信息

Microb Pathog. 2025 Mar;200:107286. doi: 10.1016/j.micpath.2025.107286. Epub 2025 Jan 8.

DOI:10.1016/j.micpath.2025.107286
PMID:39793676
Abstract

Peri-implantitis associated with dental implants shares characteristics with destructive periodontal diseases. Both conditions are multifactorial and strongly correlated with the presence of microorganisms surrounding the prostheses or natural dentition. This study aimed to evaluate the antimicrobial activity and toxicity of a mucoadhesive hydrogel functionalized with aminochalcone (HAM-15) against Aggregatibacter actinomycetemcomitans, Fusobacterium periodonticum, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Candida albicans. Various experiments were conducted to determine the minimum inhibitory concentrations (MIC) and minimum bactericidal/fungicidal concentrations (MBC/MFC), as well as the antibiofilm potential and toxicity in human gingival fibroblasts and a G. mellonella animal model. Infection and treatment studies were also performed in G. mellonella. The results demonstrated that both aminochalcone (AM-15) and the aminochalcone-functionalized hydrogel (HAM-15) exhibited antimicrobial activity, with MICs ranging from 7.8 to 31.2 μg/mL for the tested strains. Treatment with HAM-15 at 300 μg/mL reduced the monospecies biofilm of C. albicans and P. gingivalis by 7 log and 6 log, respectively, and the mixed-species biofilm of these microorganisms by 7 log and 8 log, respectively. Regarding toxicity, HAM-15 showed cytotoxic effects on human gingival fibroblasts at high concentrations, but in the G. mellonella model, survival was 70 % at a dose of 1 mg/mL. Additionally, AM-15, when administered after larval infection, protected 90 % of the animals (p < 0.05). These results suggest that AM-15 is a promising candidate for the prevention and treatment of anaerobic infections and yeasts, demonstrating significant antimicrobial efficacy and an acceptable safety profile in experimental models.

摘要

与牙种植体相关的种植体周围炎与破坏性牙周疾病具有共同特征。这两种情况都是多因素的,并且与假体或天然牙列周围微生物的存在密切相关。本研究旨在评估用氨基查尔酮功能化的粘膜粘附水凝胶(HAM-15)对伴放线聚集杆菌、牙周梭杆菌、中间普氏菌、牙龈卟啉单胞菌、福赛坦氏菌和白色念珠菌的抗菌活性和毒性。进行了各种实验以确定最低抑菌浓度(MIC)和最低杀菌/杀真菌浓度(MBC/MFC),以及在人牙龈成纤维细胞和家蚕动物模型中的抗生物膜潜力和毒性。还在家蚕中进行了感染和治疗研究。结果表明,氨基查尔酮(AM-15)和氨基查尔酮功能化水凝胶(HAM-15)均表现出抗菌活性,受试菌株的MIC范围为7.8至31.2μg/mL。用300μg/mL的HAM-15处理分别使白色念珠菌和牙龈卟啉单胞菌的单菌种生物膜减少7个对数和6个对数,使这些微生物的混合菌种生物膜分别减少7个对数和8个对数。关于毒性,HAM-15在高浓度下对人牙龈成纤维细胞显示出细胞毒性作用,但在家蚕模型中,在1mg/mL的剂量下存活率为70%。此外,AM-15在幼虫感染后给药时,保护了90%的动物(p<0.05)。这些结果表明,AM-15是预防和治疗厌氧感染及酵母菌的有前景的候选物,在实验模型中显示出显著的抗菌功效和可接受的安全性。

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