Peptide-modified nanoparticles inhibit formation of biofilms with .

PURPOSE

The interaction of g with commensal streptococci promotes colonization of the oral cavity. We previously showed that a synthetic peptide (BAR) derived from potently inhibited the formation of biofilms (IC =1.3 µM) and reduced virulence in a mouse model of periodontitis. Thus, BAR represents a novel therapeutic to control periodontitis by limiting colonization of the oral cavity. Here, we sought to develop drug-delivery vehicles for potential use in the oral cavity that comprise BAR-modified poly(lactic-co-glycolic)acid (PLGA) nanoparticles (NPs).

METHODS

PLGA-NPs were initially modified with palmitylated avidin and subsequently conjugated with biotinylated BAR. The extent of BAR modification was quantified using a fluorescent-labeled peptide. Inhibition of adherence to by BAR-modified NPs was compared with free peptide using a two-species biofilm model.

RESULTS

BAR-modified NPs exhibited an average size of 99±29 nm and a more positive surface charge than unmodified NPs (zeta potentials of -7 mV and -25 mV, respectively). Binding saturation occurred when 37 nmol BAR/mg of avidin-NPs was used, which resulted in a payload of 7.42 nmol BAR/mg NPs. BAR-modified NPs bound to in a dose-dependent manner and more potently inhibited adherence and biofilm formation relative to an equimolar amount of free peptide (IC of 0.2 µM versus 1.3 µM). BAR-modified NPs also disrupted the preformed biofilms more effectively than free peptide. Finally, we demonstrate that BAR-modified NPs promoted multivalent association with , providing an explanation for the increased effectiveness of NPs.

CONCLUSION

These results indicate that BAR-modified NPs deliver a higher local dose of peptide and may represent a more effective therapeutic approach to limit colonization of the oral cavity compared to treatment with formulations of free peptide.