Assessing efficiency of synthetic peptide-containing spray in combination therapy of chronic generalized periodontitis

Abstract

Antibacterial drugs are routinely used in therapy of periodontal diseases. However, increasing incidence of antibiotics resistance necessitates development of novel therapeutic approaches for oral diseases. Currently, newly designed antibacterial agents based on natural, semi-synthetic and synthetic peptides is the most promising approach in dentistry. Among them is a product containing synthetic peptide (ZP2) replicating active site of granulocyte-macrophage colonystimulating factor (GM-CSF) as the main active ingredient in Atsegram-spray (manufactured by Academic Innovation Research Center, Chelyabinsk). Our study was aimed at assessing efficacy of a combination therapy of inflammatory periodontal diseases by introducing Atsegram-spray as well as examining potential relationship between peptide ZP2-related biological properties, physicochemical properties of the spray and mechanism of antibacterial and immunotropic action for substantiating its application on oral mucosa. During the first stage experiments, it was found that the peptide ZP2 was able to trigger lymphocyte blast transformation in vitro indicating that it might influence cell proliferation and exhibit marked immunotropic activity. Next, we assessed potential effects of the peptide ZP2 on biofilm formation mediated by staphylococcal clinical isolates. It was shown that peptide ZP2 inhibited biofilm formation in 75.0±9.0% of S. aureus and 50.0±15.1% of S. epidermidis strains, with mean inhibition index of biofilm formation reaching 25.1±3.8 and 50.4±6.0%, respectively. However, peptide ZP2 in 8.3–25.0% of staphylococcal clinical isolates was found to stimulate/lack effect on biofilm formation by 14.9–48.5 and 16.7–25.0% cultures, respectively. Thus, the synthetic peptide ZP2 exerts divergent, but mainly inhibitory effects on biofilm formation with staphylococcal clinical strains, which are characterized by inter- and intraspecific (strain) variability. Use of a synthetic peptide-based spray in antibacterial therapy of mild chronic generalized periodontitis (main group) one month after the onset was found to improve oral hygiene by 28.5% as well as decrease PMA index and gum bleeding index by 82.8 and 100%, respectively. In contrast, such parameters in patients receiving basic therapy (comparison group) were lower on average by 2-fold. While analyzing physicochemical properties of the spray such as pH, buffer capacity and solution osmotic pressure, it was found that they were related to the antibacterial mechanism of drug activity and efficacy in treatment of inflammatory periodontal diseases. Thus, assessing peptide ZP2-related biological properties and physicochemical parameters of the spray allows to evaluate their role in mechanism of previously unknown antibacterial and immunotropic activity. These findings confirm feasibility and efficacy of using Atsegram-spray in dentistry as an alternative means to antimicrobial agents, such as antibacterial drugs.