Date on Master's Thesis/Doctoral Dissertation

5-2018

Document Type

Master's Thesis

Degree Name

M.S.

Department

Oral Biology

Degree Program

Oral Biology, MS

Committee Chair

Demuth, Donald

Committee Co-Chair (if applicable)

Steinbach-Rankins, Jill

Committee Member

Scott, David A.

Author's Keywords

electrospun fibers; electrospinning; porphyromonas gingivalis; polymers; BAR peptide; periodontitis

Abstract

Periodontitis is a chronic inflammatory disease that infects the tissues of the periodontium. It is estimated that 47.2% or 67.2 million American adults suffer from mild, moderate and severe periodontitis. Globally, 30-50% of the adult population is afflicted with periodontal disease, making it one of the most prevalent infectious diseases in the world. Therapeutics targeting P. gingivalis may be effective to alter periodontitis progression. However, the current treatment modalities that target critical pathogens to maintain host-biofilm homeostasis are limited, urging the development of specifically targeted therapeutics to limit P. gingivalis recolonization of the oral cavity after periodontal treatment and healing. We previously identified a peptide (BAR) that inhibits the formation of P. gingivalis-S. gordonii biofilms; however, formulations that effectively deliver the peptide within the oral cavity are lacking. Polymeric electrospun fibers (EFs) offer a new platform to deliver high localized concentrations of the peptide (BAR) for prolonged periods, to disrupt established biofilms and enhance BAR effectiveness. The objective of this study was to determine if electrospun fibers (EFs) that encapsulate the BAR peptide, function as a sustained-release drug delivery vehicle for application in the oral cavity. A variety of polymer formulations were electrospun using a uniaxial electrospinning approach. Polymers including poly(lactic-co-glycolic acid) (PLGA) or methoxy-poly(ethylene glycol) (mPEG-PLGA), polycaprolactone (PCL), and poly(L-lactic acid) PLLA, were synthesized alone or blended in a 40:60, 20:80 and 10:90 w/w ratio with a hydrophilic polymer, polyethylene oxide (PEO), to increase BAR release over 24 hr. To determine the total loading of BAR in EFs, the fibers were dissolved in DMSO, and the amount of BAR encapsulated was compared to a known standard of fluorescently-labeled BAR (F-BAR). The sustained-release of F-BAR from fibers was determined by comparing the supernatant from a variety of release time points to a known standard of F-BAR. PLGA, mPEG-PLGA, PCL and PLLA EFs demonstrated encapsulation efficiencies of 68%, 94% 60% and 46% respectively, while exhibiting minimal release of BAR (9.5%, 7%, 1.4% and 1.5%) within 24 hr. Blended polymeric fibers comprised of PLGA:PEO, PCL:PEO, and PLLA:PEO with 40:60, 20:80 and 10:90 w/w ratios were fabricated to enhance release. All polymer blends incorporated high concentrations of BAR peptide, and increasing ratios of PEO significantly enhanced BAR release within 24 hr. The most promising 10:90 PLGA:PEO, PCL:PEO, and PLLA:PEO formulations provided 95%, 50% and 75% BAR release at 4 hr.

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