Thermoresponsive hydrogel as a reservoir for intelligent nanoparticles controlled release of amoxicillin and metronidazole: a new therapy for controlling peri-implant infections

• Grant number: 24/06635-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2025
• End date: February 29, 2028
• Field of knowledge: Health Sciences - Dentistry - Dental Materials
• Principal Investigator: Valentim Adelino Ricardo Barão
• Grantee: Cícero Andrade Sigilião Celles
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

The presence of a pathogenic dysbiotic peri-implant biofilm with inflammation of the soft tissues and progressive bone loss in the tissues surrounding the dental implants constitutes peri-implantitis, the cause of most dental implant failure and loss. The lack of consensus on the best treatment reveals the ineffectiveness of commonly used therapies, such as mechanical debridement and systemic antibiotics, given the high rates of bacterial resistance. With their dynamic structure, hydrogels are promising biomaterials for local, controlled, and sustained drug delivery, capable of carrying environmentally-dependent nanoparticles that contribute to a multifunctional system with therapeutic safety. This study aims to develop a new therapeutic approach to control peri-implantitis using a thermoresponsive hydrogel based on poly(N-vinylcaprolactam) (PNVCL), loaded with the antibiotics amoxicillin (AMX) and metronidazole (MTZ) encapsulated in Zeolitic Imidazole Nanoparticles (ZIFs), for controlled release and targeted antimicrobial action. Four groups will be evaluated: (1) PNVCL (control), (2) PNVCL + ZIFs-AMX, (3) PNVCL + ZIFs-MTZ, and (4) PNVC + ZIFs-AMX + ZIFs-MTZ. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the drugs AMX and MTZ will be determined and 5×MBC will be used in the synthesis of the ZIFs, which will be evaluated for morphology by scanning electron microscopy (SEM), encapsulation efficiency and loading capacity. After the synthesis of the hydrogel, its morphology will be evaluated by SEM, interaction, and functionality by Fourier Transform Infrared Spectroscopy (FTIR), critical solution temperature, gelation time, rheological properties, mass distribution by gel permeation chromatography, adhesion, degree of swelling, degradation and release of AMX and MTZ by high performance liquid chromatography. The antimicrobial activity will be evaluated using a polymicrobial biofilm model (microcosm) developed on the surface of dental implants fixed in positioners to simulate the bone resorption present in peri-implantitis and confirmation of these effects in situ with oral application of the hydrogel in disks placed in palatal devices that volunteers will use. After in vitro and in situ experiments the following analysis will be performed colony-forming units (CFU), biofilm morphology by SEM, cell viability by confocal laser scanning microscopy (CLSM), and microbial composition by DNA-DNA checkerboard. Qualitative and quantitative analyses will be carried out to confirm the absence of hydrogel toxicity when in contact with gingival fibroblast cells and MC3T3-E1 pre-osteoblastic cells, by analyzing CCK-8, metabolic activity by MTT, cell viability (Live/Dead) and fluorescence microscopy. The data will be statistically analyzed at a significance level of 0.05.