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Polysaccharide Formulations for Localized Nitric Oxide Delivery.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Polysaccharide Formulations for Localized Nitric Oxide Delivery./
Author:	Feura, Evan Scott.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
Description:	175 p.
Notes:	Source: Dissertations Abstracts International, Volume: 82-08, Section: B.
Contained By:	Dissertations Abstracts International82-08B.
Subject:	Polymer chemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28157905
ISBN:	9798557082808

Polysaccharide Formulations for Localized Nitric Oxide Delivery.
Feura, Evan Scott.

Polysaccharide Formulations for Localized Nitric Oxide Delivery. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 175 p.

Source: Dissertations Abstracts International, Volume: 82-08, Section: B.

Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2020.

This item is not available from ProQuest Dissertations & Theses.

Periodontal diseases (i.e., gingivitis and periodontitis) are among the most common diseases affecting mankind and represent a severe burden on healthcare expenditure, quality of life, and systemic health. Dysbiotic dental plaque biofilms, which drive periodontal disease progression through immune stimulation, are difficult to treat due to biofilm protective mechanisms and the isolating effects of periodontal pockets. Nitric oxide (NO), an endogenous inflammatory modulator and antimicrobial agent, has demonstrated promise against dental plaque biofilms due to its multiple mechanisms of antibacterial activity. The high reactivity of NO necessitates the development of formulations that facilitate local delivery in order to maximize NO's therapeutic efficacy.Carboxymethylcellulose (CMC), a polysaccharide with ideal characteristics for local delivery (e.g., inherent mucoadhesive properties and high solution viscosity), was derivatized into an NO-releasing polymer via modification with four alkylamines. The NO-releasing CMCs possessed a range of NO-release kinetics and demonstrated antibacterial activity against the planktonic periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. The biopolymers were not toxic against human gingival fibroblasts at their bactericidal concentrations, supporting their potential as periodontal disease therapeutics.In addition to the development of a novel NO-release scaffold, a polysaccharide-based hydrogel delivery formulation was explored for improving local delivery of NO-releasing hyperbranched polyamidoamine (hPAMAM-NO). Eradication of oral bacteria and mitigation of periodontal bone loss by hPAMAM-NO formulations were evaluated in a murine model of periodontitis. Control and NO-releasing hydrogels demonstrated significantly decreased aerobic bacterial counts. Reductions in bone loss were observed in mice treated with acidified hPAMAM-NO solution, suggesting that further optimization of hydrogel formulations is necessary to maximize local retention and effective delivery of NO.Injectable polysaccharide hydrogels prepared from ~100 kDa amine-modified CMC, hyaluronic acid (HA), and dextran were systematically evaluated using oscillatory shear rheology, swelling, degradation, and cytotoxicity studies. All evaluated hydrogels demonstrated compatibility with multiple NO donors, and the impact of hydrogels on NO-release kinetics were dependent on the NO donor identity. The CMC hydrogels were most tolerant of NO donor loading into the hydrogels, while HA hydrogels had the greatest swelling capacity. These versatile scaffolds represent a promising biocompatible platform for localized NO delivery.

ISBN: 9798557082808Subjects--Topical Terms:

3173488
Polymer chemistry.
Subjects--Index Terms:

Hydrogel

Polysaccharide Formulations for Localized Nitric Oxide Delivery.
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100 1 $a Feura, Evan Scott. $3 3687059
245 1 0 $a Polysaccharide Formulations for Localized Nitric Oxide Delivery.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 175 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-08, Section: B.
500 $a Advisor: Schoenfisch, Mark H.;You, Wei.
502 $a Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2020.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be sold to any third party vendors.
520 $a Periodontal diseases (i.e., gingivitis and periodontitis) are among the most common diseases affecting mankind and represent a severe burden on healthcare expenditure, quality of life, and systemic health. Dysbiotic dental plaque biofilms, which drive periodontal disease progression through immune stimulation, are difficult to treat due to biofilm protective mechanisms and the isolating effects of periodontal pockets. Nitric oxide (NO), an endogenous inflammatory modulator and antimicrobial agent, has demonstrated promise against dental plaque biofilms due to its multiple mechanisms of antibacterial activity. The high reactivity of NO necessitates the development of formulations that facilitate local delivery in order to maximize NO's therapeutic efficacy.Carboxymethylcellulose (CMC), a polysaccharide with ideal characteristics for local delivery (e.g., inherent mucoadhesive properties and high solution viscosity), was derivatized into an NO-releasing polymer via modification with four alkylamines. The NO-releasing CMCs possessed a range of NO-release kinetics and demonstrated antibacterial activity against the planktonic periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. The biopolymers were not toxic against human gingival fibroblasts at their bactericidal concentrations, supporting their potential as periodontal disease therapeutics.In addition to the development of a novel NO-release scaffold, a polysaccharide-based hydrogel delivery formulation was explored for improving local delivery of NO-releasing hyperbranched polyamidoamine (hPAMAM-NO). Eradication of oral bacteria and mitigation of periodontal bone loss by hPAMAM-NO formulations were evaluated in a murine model of periodontitis. Control and NO-releasing hydrogels demonstrated significantly decreased aerobic bacterial counts. Reductions in bone loss were observed in mice treated with acidified hPAMAM-NO solution, suggesting that further optimization of hydrogel formulations is necessary to maximize local retention and effective delivery of NO.Injectable polysaccharide hydrogels prepared from ~100 kDa amine-modified CMC, hyaluronic acid (HA), and dextran were systematically evaluated using oscillatory shear rheology, swelling, degradation, and cytotoxicity studies. All evaluated hydrogels demonstrated compatibility with multiple NO donors, and the impact of hydrogels on NO-release kinetics were dependent on the NO donor identity. The CMC hydrogels were most tolerant of NO donor loading into the hydrogels, while HA hydrogels had the greatest swelling capacity. These versatile scaffolds represent a promising biocompatible platform for localized NO delivery.
590 $a School code: 0153.
650 4 $a Polymer chemistry. $3 3173488
650 4 $a Materials science. $3 543314
650 4 $a Immunology. $3 611031
650 4 $a Public health. $3 534748
650 4 $a Pathology. $3 643180
650 4 $a Dentistry. $3 828971
650 4 $a Health care management. $3 2122906
650 4 $a Organic chemistry. $3 523952
653 $a Hydrogel
653 $a Nitric oxide
653 $a Periodontal disease
653 $a Polysaccharide
653 $a Therapeutic
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690 $a 0490
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710 2 $a The University of North Carolina at Chapel Hill. $b Chemistry. $3 1021872
773 0 $t Dissertations Abstracts International $g 82-08B.
790 $a 0153
791 $a Ph.D.
792 $a 2020
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28157905