BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilms
Abstract Background Porphyromonas gingivalis adherence to oral streptococci is a key point in the pathogenesis of periodontal diseases (Honda in Cell Host Microbe 10:423–425, 2011). Previous work in our groups has shown that a region of the streptococcal antigen denoted BAR (SspB Adherence Region) i...
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-018-0396-4 |
| _version_ | 1798041865477423104 |
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| author | Mohamed Y. Mahmoud Donald R. Demuth Jill M. Steinbach-Rankins |
| author_facet | Mohamed Y. Mahmoud Donald R. Demuth Jill M. Steinbach-Rankins |
| author_sort | Mohamed Y. Mahmoud |
| collection | DOAJ |
| description | Abstract Background Porphyromonas gingivalis adherence to oral streptococci is a key point in the pathogenesis of periodontal diseases (Honda in Cell Host Microbe 10:423–425, 2011). Previous work in our groups has shown that a region of the streptococcal antigen denoted BAR (SspB Adherence Region) inhibits P. gingivalis/S. gordonii interaction and biofilm formation both in vitro and in a mouse model of periodontitis (Daep et al. in Infect Immun 74:5756–5762, 2006; Daep et al. in Infect immun 76:3273–3280, 2008; Daep et al. in Infect Immun 79:67–74, 2011). However, high localized concentration and prolonged exposure are needed for BAR to be an effective therapeutic in the oral cavity. Methods To address these challenges, we fabricated poly(lactic-co-glycolic acid) (PLGA) and methoxy-polyethylene glycol PLGA (mPEG-PLGA) nanoparticles (NPs) that encapsulate BAR peptide, and assessed the potency of BAR-encapsulated NPs to inhibit and disrupt in vitro two-species biofilms. In addition, the kinetics of BAR-encapsulated NPs were compared after different durations of exposure in a two-species biofilm model, against previously evaluated BAR-modified NPs and free BAR. Results BAR-encapsulated PLGA and mPEG-PLGA NPs potently inhibited biofilm formation (IC50 = 0.7 μM) and also disrupted established biofilms (IC50 = 1.3 μM) in a dose-dependent manner. In addition, BAR released during the first 2 h of administration potently inhibits biofilm formation, while a longer duration of 3 h is required to disrupt pre-existing biofilms. Conclusions These results suggest that BAR-encapsulated NPs provide a potent platform to inhibit (prevent) and disrupt (treat) P. gingivalis/S. gordonii biofilms, relative to free BAR. |
| first_indexed | 2024-04-11T22:27:32Z |
| format | Article |
| id | doaj.art-8a5a4140bd564c1195338b3443c0618d |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T22:27:32Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-8a5a4140bd564c1195338b3443c0618d2022-12-22T03:59:37ZengBMCJournal of Nanobiotechnology1477-31552018-09-0116111210.1186/s12951-018-0396-4BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilmsMohamed Y. Mahmoud0Donald R. Demuth1Jill M. Steinbach-Rankins2Department of Pharmacology and Toxicology, University of Louisville School of MedicineDepartment of Oral Immunology and Infectious Diseases, University of Louisville School of DentistryDepartment of Bioengineering, University of Louisville Speed School of EngineeringAbstract Background Porphyromonas gingivalis adherence to oral streptococci is a key point in the pathogenesis of periodontal diseases (Honda in Cell Host Microbe 10:423–425, 2011). Previous work in our groups has shown that a region of the streptococcal antigen denoted BAR (SspB Adherence Region) inhibits P. gingivalis/S. gordonii interaction and biofilm formation both in vitro and in a mouse model of periodontitis (Daep et al. in Infect Immun 74:5756–5762, 2006; Daep et al. in Infect immun 76:3273–3280, 2008; Daep et al. in Infect Immun 79:67–74, 2011). However, high localized concentration and prolonged exposure are needed for BAR to be an effective therapeutic in the oral cavity. Methods To address these challenges, we fabricated poly(lactic-co-glycolic acid) (PLGA) and methoxy-polyethylene glycol PLGA (mPEG-PLGA) nanoparticles (NPs) that encapsulate BAR peptide, and assessed the potency of BAR-encapsulated NPs to inhibit and disrupt in vitro two-species biofilms. In addition, the kinetics of BAR-encapsulated NPs were compared after different durations of exposure in a two-species biofilm model, against previously evaluated BAR-modified NPs and free BAR. Results BAR-encapsulated PLGA and mPEG-PLGA NPs potently inhibited biofilm formation (IC50 = 0.7 μM) and also disrupted established biofilms (IC50 = 1.3 μM) in a dose-dependent manner. In addition, BAR released during the first 2 h of administration potently inhibits biofilm formation, while a longer duration of 3 h is required to disrupt pre-existing biofilms. Conclusions These results suggest that BAR-encapsulated NPs provide a potent platform to inhibit (prevent) and disrupt (treat) P. gingivalis/S. gordonii biofilms, relative to free BAR.http://link.springer.com/article/10.1186/s12951-018-0396-4Polymer nanoparticlePoly(lactic-co-glycolic acid)Peptide deliveryDrug deliveryPorphyromonas gingivalisStreptococcus gordonii |
| spellingShingle | Mohamed Y. Mahmoud Donald R. Demuth Jill M. Steinbach-Rankins BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilms Journal of Nanobiotechnology Polymer nanoparticle Poly(lactic-co-glycolic acid) Peptide delivery Drug delivery Porphyromonas gingivalis Streptococcus gordonii |
| title | BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilms |
| title_full | BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilms |
| title_fullStr | BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilms |
| title_full_unstemmed | BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilms |
| title_short | BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilms |
| title_sort | bar encapsulated nanoparticles for the inhibition and disruption of porphyromonas gingivalis streptococcus gordonii biofilms |
| topic | Polymer nanoparticle Poly(lactic-co-glycolic acid) Peptide delivery Drug delivery Porphyromonas gingivalis Streptococcus gordonii |
| url | http://link.springer.com/article/10.1186/s12951-018-0396-4 |
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