Efficacy of drugs associated with nanotechnology for control of cariogenic biofilms

Abstract

The development of effective therapies for oral biofilm control is challenging. Topical agents used to treat and prevent oral diseases are not kept in the mouth for a sufficient time; consequently, they can't exert their maximum therapeutic potential. Therefore, Nanoparticles Carrier (NPC) for drug delivery were developed that bind to the surface of hydroxyapatite (the main mineral of teeth), salivary pellicle and exopolysaccharides (main components of cariogenic biofilm' extracellular matrix). These NPCs have responsive elements to pH changes controlling the release of a drug into acidic niches found in pathogenic biofilms. For example, tt-farnesol (a drug that can hinder Streptococcus mutans virulence factors) can be successfully loaded and released by NPCs. The mixed-species biofilm of S. mutans and Candida albicans is extremely pathogenic, with rapid structural development and increased production of matrix rich in exopolysaccharides and of acids via metabolism of dietary sugars. Hence, the objective is to investigate whether the association with other drugs would help tt-farnesol loaded into NPCs to better control cariogenic biofilm, reducing the pathogenic potential by acting on more virulence factors. Thus, the NPCs will be modified (chemistry and structure) to carry other drugs (i.e., myricetin and fluoride) to perform topical treatments of mixed pathogenic biofilms. The efficacy of the treatments will be demonstrated by microbiological tests (counting of colony forming units), assessment of virulence gene expression of (via RT-qPCR of 9 bacteria and 10 fungi genes), biochemical assays (characterization of extracellular matrix) and confocal microscopy (biofilm's 3D architecture). Statistical tests will be applied according to distribution to interpret the results, adopting a 5% significance level. It is expected to understand how the biofilms react to the proposed treatments, aiming to reduce virulence. (AU)