Efficacy of drugs delivered by pH-activated nanocarriers to prevent dental caries

• Grant number: 24/07546-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Marlise Inêz Klein Furlan
• Grantee: Mateus Xavier de Queiroz
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
• Associated research grant: 21/06801-1 - Extracellular matrix: from biology to strategies for controlling cariogenic biofilms, AP.JP2

Abstract

Controlling dental biofilms can prevent the occurrence of caries disease, as this disease is mediated by biofilm and modulated by dietary sugars. The biofilm control is commonly done by mechanical (partial) removal of the biofilm via brushing and dental floss/tape. Still, some individuals do not have manual dexterity or have some condition that interferes with the adequate performance of these conventional oral hygiene procedures. Thus, it is necessary to use adjuvant strategies that help control biofilm. In its different presentations, fluoride is used to minimize the demineralization process. Several substances (or compounds) with antimicrobial activity (i.e., capable of inhibiting microbial growth or killing microorganisms) and/or biofilm activity (e.g., capable of inhibiting or delaying the adhesion of microorganisms or interfering with the construction of the extracellular matrix). However, the substances need to remain in the oral cavity long enough to have an effect. Hence, different drug carrier systems have been developed, among which pH-activated nanocarriers have the advantage of releasing drugs when the environment becomes acidic (a result of microbial metabolism), which is a determinant for dental demineralization. Therefore, the objective is to examine the efficacy of molecules associated with nanotechnology for preventing dental caries in vivo. An in situ study will be carried out with 16 participants using a model with palatal apparatus with dental blocks, crossed, with 4 phases and washout periods and topical application of sucrose+starch solution to form cariogenic biofilm). Participants will use solutions for topical application: (1) test formulation (nanocarriers + drugs), (2) test formulation vehicle control, (3) sodium fluoride as a remineralization positive control, and (4) antimicrobial digluconate as a positive control of chlorhexidine. Biofilm analyses will include: (a) the evaluation of the matrix (chemical/molecular composition, including resistome markers in the extracellular); (b) the determination of the microbiota (DNA-seq for bacteria and fungi) and their expressed metabolic pathways (RNA-seq, detection of resistome markers in the intracellular DNA); (c) quantification of calcium and phosphate; and (d) structural characterization. The dental demineralization of the dental blocks will also be evaluated. The data will be analyzed using statistical and bioinformatics tools (databases) and compared with the literature.