International Journal of Nanomedicine (Jun 2017)
Peptide-modified nanoparticles inhibit formation of Porphyromonas gingivalis biofilms with Streptococcus gordonii
Abstract
Paridhi Kalia,1 Ankita Jain,1 Ranjith Radha Krishnan,1 Donald R Demuth,1,2 Jill M Steinbach-Rankins2–5 1Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, 2Department of Microbiology and Immunology, University of Louisville School of Medicine, 3Department of Bioengineering, University of Louisville Speed School of Engineering, 4Department of Pharmacology and Toxicology, University of Louisville School of Medicine, 5Center for Predictive Medicine, University of Louisville, Louisville, KY, USA Purpose: The interaction of Porphyromonas gingivalis with commensal streptococci promotes P. gingivalis colonization of the oral cavity. We previously showed that a synthetic peptide (BAR) derived from Streptococcus gordonii potently inhibited the formation of P. gingivalis/S. gordonii biofilms (IC50 =1.3 µM) and reduced P. gingivalis virulence in a mouse model of periodontitis. Thus, BAR represents a novel therapeutic to control periodontitis by limiting P. gingivalis 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 P. gingivalis adherence to S. gordonii 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 P. gingivalis in a dose-dependent manner and more potently inhibited P. gingivalis/S. gordonii adherence and biofilm formation relative to an equimolar amount of free peptide (IC50 of 0.2 µM versus 1.3 µM). BAR-modified NPs also disrupted the preformed P. gingivalis/S. gordonii biofilms more effectively than free peptide. Finally, we demonstrate that BAR-modified NPs promoted multivalent association with P. gingivalis, 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 P. gingivalis colonization of the oral cavity compared to treatment with formulations of free peptide. Keywords: nanoparticle, peptide delivery, multivalent, drug delivery, Porphyromonas gingivalis, periodontal disease
