Abstract
Active agents targeting key bacterial interactions that initiate biofilm formation in the oral cavity, may alter periodontitis progression; however, to date, specifically-targeted prophylactic and treatment strategies have been limited. Previously we developed a peptide, BAR (SspB Adherence Region), that inhibits oral P. gingivalis/S. gordonii biofilm formation in vitro and in vivo, and BAR nanoparticles that increase BAR effectiveness via multivalency and prolonged delivery. However, limited BAR loading and nanoparticle retention in the oral cavity can result in inadequate release and efficaciousness. Given this, an effective delivery platform that can release concentrations of BAR suitable for twice-daily applications, may offer an alternative that enhances loading, ease of administration, and retention in the oral cavity. With this in mind, the study objectives were to develop and characterize a rapid-release platform, composed of polymeric electrospun fibers (EFs) that encapsulate BAR, and to evaluate fiber safety and functionality against P. gingivalis/S. gordonii biofilms in vitro. Poly(lactic-co-glycolic acid) (PLGA), poly(L-lactic acid) (PLLA), and polycaprolactone (PCL) were electrospun alone or blended with polyethylene oxide (PEO), to provide high BAR loading and rapid-release. The most promising formulation, 10:90 PLGA:PEO EFs, provided 95% BAR release after 4 h, dose-dependent inhibition of biofilm formation (IC50 = 1.3 μM), disruption of established dual-species biofilms (IC50 = 2 μM), and maintained high cell viability. These results suggest that BAR-incorporated EFs may provide a safe and specifically-targeted rapid-release platform to inhibit and disrupt dual-species biofilms, that we envision may be applied twice-daily to exert prophylactic effect in the oral cavity.
Highlights
Periodontal disease is a group of chronic inflammatory diseases that are globally prevalent, affecting over 65 million adults in the U.S, with increased incidence in developing countries
We proposed that the development of an effective oral delivery system that can release BAR within a time frame desired for twice-daily applications, may offer an alternative platform that increases loading, facilitates ease of administration, and provides the potential of enhanced retention in the oral cavity
The total fluorescent BAR peptide (F-BAR) loading for non-blended and blended electrospun fibers (EFs) ranged between 4.6 and 6.9 μg BAR/mg polymer and 6.0–9.2 μg BAR/mg polymer, respectively, indicating that high loading of F-BAR was achieved in all fiber formulations (Table 1)
Summary
Periodontal disease is a group of chronic inflammatory diseases that are globally prevalent, affecting over 65 million adults in the U.S, with increased incidence in developing countries. While the primary niche of P. gingivalis is the anaerobic environment of the subgingival pocket, P. gingivalis initially colonizes the oral cavity by interacting with Gram-positive commensal streptococci in the supragingival environment (Marsh, 1994). These initial adhesive interactions represent ideal points for intervention to prevent P. gingivalis colonization and can be targeted with designed biologics that may effectively curtail the progression of periodontal disease (Daep et al, 2006)
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