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Suitability and effect of a controlled drug release system in presence of patogenic biofilm


Biolfim is the etiologic factor for most oral diseases such as caries, gingivitis and periodontitis. Thus, the control of biofilm can help to decrease such diseases. A number of studies have been conducted in order to develop products containing antimicrobials that can interfere on this mechanism. In this sense, controlled drug delivery systems (DDS) have been developed to be used in the oral cavity. Nevertheless, few studies deal with the evaluation of such systems using models that mimics the oral environment, including the presence of bacteria organized in biofilm. Thus, this work aims at evaluate an in vitro model that includes the main challenges that a drug delivery system needs to envisage in order to be successfully applied in the oral cavity. In the first part of the study a drug delivery system to be applied in the mouth will be obtained. The system was idealized in order to be able to overcome the presence of bacteria, their extracellular products, occurring in a liquid medium that will be changed daily. For that purpose, an in situ gelling system made of glycerol monooleate will be prepared and submitted to a previous evaluation in order to adapt the system to the conditions of the biofilm model. In the second part of the study, the DDS will be challenged in the presence of Streptococcus mutans or Porphyromonas gingivalis biofilms, cultivated in culture medium tubes containing glass slides. The following conditions will be studied: 1) DDS without drug, as negative control; 2) DDS containing 0.12% of chlorhexidine, as positive control; 3) DDS containing metronidazole; 4) DDS containing a hydroethanolic extract of Baccharis dracunculifolia, a natural product with promising activity against planktonic cells. The acidogenicity of the biofilms and the amount of drug released will be evaluated daily. After the growing of biofilms, they will be collected and homogenized by sonication. Bacterial viability will be monitored by means of bacterial counting in blood agar. Extracellular polysaccharide will be extracted and analyzed and the amount of drug in the biofilms will be quantified using an HPLC. At the end of the study, the amount of DDS remaining will be weighted and its crystalline organization and amount of residual drug will be analyzed. The data analysis will include an initial evaluation of homogeneity and variability of the set of data. If data shows a normal distribution, analysis of variance (ANOVA) and a post-hoc test will be applied. If the data does not follow a normal distribution, the Kruskal-Wallis test will be used instead. The level of significance of 5% will be accepted. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RE, A. C. S.; FERREIRA, M. P.; FREITAS, O.; AIRES, C. P. Antimicrobial effect of a local release system containing metronidazole against a Porphyromonas gingivalis biofilm. Pharmazie, v. 74, n. 11, p. 665-666, NOV 2019. Web of Science Citations: 0.
RE, A. C. S.; FERREIRA, M. P.; FREITAS, O.; AIRES, C. P. Local antibiotic delivery in periodontitis: drug release and its effect on supragingival biofilms. BIOFOULING, v. 32, n. 9, p. 1061-1066, 2016. Web of Science Citations: 4.

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