Functional assessment of peptide-modified PLGA nanoparticles against oral biofilms in a murine model of periodontitis

Abstract

The interaction of the periodontal pathogen Porphyromonas gingivalis (Pg) with commensal streptococci promotes Pg colonization of the oral cavity. Previously, we demonstrated that a peptide (BAR) derived from Streptococcus gordonii (Sg) potently inhibited adherence of Pg to streptococci and reduced Pg virulence in a mouse model of periodontitis. Thus, BAR may represent a novel therapeutic to control periodontitis by preventing Pg colonization of the oral cavity. However, while BAR inhibited the initial formation of Pg/Sg biofilms, much higher concentrations of peptide were required to disrupt an established Pg/Sg biofilm. To improve the activity of the peptide, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were surface-modified with BAR and shown to more potently disrupt Pg/Sg biofilms relative to an equimolar amount of free peptide. The goal of this work was to determine the in vivo efficacy of BAR-modified NPs (BNPs) and to assess the toxicity of BNPs against human gingival epithelial cells. In vivo efficacy of BNPs was assessed using a murine model of periodontitis by measuring alveolar bone resorption and gingival IL-17 expression as outcomes of Pg-induced inflammation. Infection of mice with Pg and Sg resulted in a significant increase in alveolar bone loss and gingival IL-17 expression over sham-infected animals. Treatment of Pg/Sg infected mice with BNPs reduced

Cyclodextrin‐Derived Intrinsically Bioactive Nanoparticles for Treatment of Acute and Chronic Inflammatory Diseases

“…Collectively, the above results substantiated that LCD NP may serve as a potential nanotherapy for the treatment of both acute and chronic inflammatory diseases resulting from neutrophil and macrophage infiltration. In addition to systemic delivery, LCD NP can be administered by local injection, such as for the treatment of periodontal disease (a set of inflammatory conditions in periodontal tissues), since previous studies have demonstrated therapeutic advantages of several nanoplatforms . Also, the periodontal treatment might be beneficial for therapy of systemic inflammatory diseases such as diabetes and atherosclerosis in view of their close link with periodontal disease .…”

Rapid Release Polymeric Fibers for Inhibition of Porphyromonas gingivalis Adherence to Streptococcus gordonii

“…The fiber solution was subsequently vortexed, sonicated for 5 min, and dissolved for 1 h in a dark room. The quantity of extracted F-BAR was determined by measuring the fluorescence using a spectrophotometer (488/518 nm excitation/emission), relative to an F-BAR standard (Kalia et al, 2017;Mahmoud et al, 2018Mahmoud et al, , 2019. A standard curve of F-BAR was obtained by adding 0.1 mg F-BAR to 1 mL of 1:9 DMSO:TE, and serially diluting in 1:9 DMSO:TE.…”

“…Telomerase immortalized gingival keratinocytes (TIGKs) were grown on 12-well collagen-coated plates (Becton Dickinson, Bedford, MA) and cultured using DermaLife K Calcium Free Medium (LifeFactors R ) supplemented with penicillin/streptomycin (100 U/mL final concentration; St. Louis, MO), insulin (5 µg/mL), recombinant human (rh), L-glutamine (6 mM), apo-transferrin (5 µg/mL), epinephrine (1 µM), rh TGF-α (0.5 ng/mL), extract P TM , calcium chloride (0.06 mM) and hydrocortisone hemisuccinate (100 ng/mL). The cells were incubated at 37 • C in the presence of 5% CO 2 for 6 days until they reached 95% confluence (Mahmoud et al, 2019).…”

“…Water replaced PBS as a positive control for cell hemolysis. The suspension was incubated at 37 • C for 3 h then centrifuged at 3,500 × g. Hemoglobin released due to cell lysis was analyzed by measuring the absorbance at 541 nm (Mahmoud et al, 2019).…”

“…We previously showed that BAR-modified and BARencapsulated nanoparticles inhibit P. gingivalis biofilm formation (Kalia et al, 2017;Mahmoud et al, 2018Mahmoud et al, , 2019. These vehicles were envisioned to serve in formulations such as an oral gel, varnish or mouthwash that require two to three daily applications.…”