Loading and Release of Quercetin from Contact-Drawn Polyvinyl Alcohol Fiber Scaffolds

Zachary B. Visser; Surendra Kumar Verma; Jan K. Rainey; John P. Frampton

doi:10.1021/acsptsci.2c00191

Loading and Release of Quercetin from Contact-Drawn Polyvinyl Alcohol Fiber Scaffolds

Zachary B. Visser, Surendra Kumar Verma, Jan K. Rainey, John P. Frampton

Medicine

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Polymeric drug releasing systems have numerous applications for the treatment of chronic diseases and traumatic injuries. In this study, a simple, cost-effective, and scalable method for dry spinning of crosslinked polyvinyl alcohol (PVA) fibers is presented. This method utilizes an entangled solution of PVA to form liquid bridges that are drawn into rapidly drying fibers through extensional flow. The fibers are crosslinked by a one-pot reaction in which glyoxal is introduced to the PVA solution prior to contact drawing. Failure analysis of fiber formation is used to understand the interplay of polymer concentration, glyoxal concentration, and crosslinking time to identify appropriate formulations for the production of glyoxal-crosslinked PVA fibers. The small molecule quercetin (an anti-inflammatory plant flavonoid) can be added to the one-pot reaction and is shown to be incorporated into the fibers in a concentration-dependent manner. Upon rehydration in an aqueous medium, the glyoxal-crosslinked PVA fiber scaffolds retain their morphology and slowly degrade, as measured over the course of 10 days. As the scaffolds degrade, they release the loaded quercetin, reaching a cumulative release of 56 ± 6% of the loaded drug after 10 days. The bioactivity of the released quercetin is verified by combining quercetin-loaded fibers with contact-drawn polyethylene oxide-type I collagen (PEO-Col) fibers and monitoring the growth of PC12 cells on the fibers. PC12 cells readily attach to the PEO-Col fibers and display increased nerve growth factor-induced elongation and neurite formation in the presence of quercetin-loaded PVA fibers relative to substrates formed from only PEO-Col fibers or PEO-Col and PVA fibers without quercetin.

Original language	English
Journal	ACS Pharmacology and Translational Science
DOIs	https://doi.org/10.1021/acsptsci.2c00191
Publication status	Accepted/In press - 2022

Bibliographical note

Funding Information:
This work was supported by funds from the Canada Research Chairs Program (J.P.F.), the Canada Foundation for Innovation (J.P.F., project #33533), the Natural Sciences and Engineering Research Council of Canada (J.P.F., RGPIN/04298-2016; J.K.R., RGPIN/05907-2017; and J.K.R. and J.P.F., RTI/000030-2020) and the New Frontiers in Research Fund (J.P.F. and J.K.R., NFRFE/2018-00356). Z.B.V. wishes to acknowledge scholarships from the Canadian Institutes of Health Research and from Research Nova Scotia (formerly the Nova Scotia Health Research Foundation). S.K.V. acknowledges salary support from a Killam Postdoctoral Fellowship. The authors acknowledge the use of the Dalhousie University Faculty of Medicine Electron Microscopy Core Facility. Finally, the authors acknowledge that Dalhousie University is located in Mi’kma’ki, the ancestral and unceded territory of the Mi’kmaq.

Publisher Copyright:
© 2022 American Chemical Society.

ASJC Scopus Subject Areas

Pharmacology
Pharmacology (medical)

PubMed: MeSH publication types

Journal Article

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10.1021/acsptsci.2c00191

Cite this

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title = "Loading and Release of Quercetin from Contact-Drawn Polyvinyl Alcohol Fiber Scaffolds",

abstract = "Polymeric drug releasing systems have numerous applications for the treatment of chronic diseases and traumatic injuries. In this study, a simple, cost-effective, and scalable method for dry spinning of crosslinked polyvinyl alcohol (PVA) fibers is presented. This method utilizes an entangled solution of PVA to form liquid bridges that are drawn into rapidly drying fibers through extensional flow. The fibers are crosslinked by a one-pot reaction in which glyoxal is introduced to the PVA solution prior to contact drawing. Failure analysis of fiber formation is used to understand the interplay of polymer concentration, glyoxal concentration, and crosslinking time to identify appropriate formulations for the production of glyoxal-crosslinked PVA fibers. The small molecule quercetin (an anti-inflammatory plant flavonoid) can be added to the one-pot reaction and is shown to be incorporated into the fibers in a concentration-dependent manner. Upon rehydration in an aqueous medium, the glyoxal-crosslinked PVA fiber scaffolds retain their morphology and slowly degrade, as measured over the course of 10 days. As the scaffolds degrade, they release the loaded quercetin, reaching a cumulative release of 56 ± 6% of the loaded drug after 10 days. The bioactivity of the released quercetin is verified by combining quercetin-loaded fibers with contact-drawn polyethylene oxide-type I collagen (PEO-Col) fibers and monitoring the growth of PC12 cells on the fibers. PC12 cells readily attach to the PEO-Col fibers and display increased nerve growth factor-induced elongation and neurite formation in the presence of quercetin-loaded PVA fibers relative to substrates formed from only PEO-Col fibers or PEO-Col and PVA fibers without quercetin.",

author = "Visser, {Zachary B.} and Verma, {Surendra Kumar} and Rainey, {Jan K.} and Frampton, {John P.}",

note = "Funding Information: This work was supported by funds from the Canada Research Chairs Program (J.P.F.), the Canada Foundation for Innovation (J.P.F., project #33533), the Natural Sciences and Engineering Research Council of Canada (J.P.F., RGPIN/04298-2016; J.K.R., RGPIN/05907-2017; and J.K.R. and J.P.F., RTI/000030-2020) and the New Frontiers in Research Fund (J.P.F. and J.K.R., NFRFE/2018-00356). Z.B.V. wishes to acknowledge scholarships from the Canadian Institutes of Health Research and from Research Nova Scotia (formerly the Nova Scotia Health Research Foundation). S.K.V. acknowledges salary support from a Killam Postdoctoral Fellowship. The authors acknowledge the use of the Dalhousie University Faculty of Medicine Electron Microscopy Core Facility. Finally, the authors acknowledge that Dalhousie University is located in Mi{\textquoteright}kma{\textquoteright}ki, the ancestral and unceded territory of the Mi{\textquoteright}kmaq. Publisher Copyright: {\textcopyright} 2022 American Chemical Society.",

year = "2022",

doi = "10.1021/acsptsci.2c00191",

language = "English",

journal = "ACS Pharmacology and Translational Science",

issn = "2575-9108",

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T1 - Loading and Release of Quercetin from Contact-Drawn Polyvinyl Alcohol Fiber Scaffolds

AU - Visser, Zachary B.

AU - Verma, Surendra Kumar

AU - Rainey, Jan K.

AU - Frampton, John P.

N1 - Funding Information: This work was supported by funds from the Canada Research Chairs Program (J.P.F.), the Canada Foundation for Innovation (J.P.F., project #33533), the Natural Sciences and Engineering Research Council of Canada (J.P.F., RGPIN/04298-2016; J.K.R., RGPIN/05907-2017; and J.K.R. and J.P.F., RTI/000030-2020) and the New Frontiers in Research Fund (J.P.F. and J.K.R., NFRFE/2018-00356). Z.B.V. wishes to acknowledge scholarships from the Canadian Institutes of Health Research and from Research Nova Scotia (formerly the Nova Scotia Health Research Foundation). S.K.V. acknowledges salary support from a Killam Postdoctoral Fellowship. The authors acknowledge the use of the Dalhousie University Faculty of Medicine Electron Microscopy Core Facility. Finally, the authors acknowledge that Dalhousie University is located in Mi’kma’ki, the ancestral and unceded territory of the Mi’kmaq. Publisher Copyright: © 2022 American Chemical Society.

PY - 2022

Y1 - 2022

N2 - Polymeric drug releasing systems have numerous applications for the treatment of chronic diseases and traumatic injuries. In this study, a simple, cost-effective, and scalable method for dry spinning of crosslinked polyvinyl alcohol (PVA) fibers is presented. This method utilizes an entangled solution of PVA to form liquid bridges that are drawn into rapidly drying fibers through extensional flow. The fibers are crosslinked by a one-pot reaction in which glyoxal is introduced to the PVA solution prior to contact drawing. Failure analysis of fiber formation is used to understand the interplay of polymer concentration, glyoxal concentration, and crosslinking time to identify appropriate formulations for the production of glyoxal-crosslinked PVA fibers. The small molecule quercetin (an anti-inflammatory plant flavonoid) can be added to the one-pot reaction and is shown to be incorporated into the fibers in a concentration-dependent manner. Upon rehydration in an aqueous medium, the glyoxal-crosslinked PVA fiber scaffolds retain their morphology and slowly degrade, as measured over the course of 10 days. As the scaffolds degrade, they release the loaded quercetin, reaching a cumulative release of 56 ± 6% of the loaded drug after 10 days. The bioactivity of the released quercetin is verified by combining quercetin-loaded fibers with contact-drawn polyethylene oxide-type I collagen (PEO-Col) fibers and monitoring the growth of PC12 cells on the fibers. PC12 cells readily attach to the PEO-Col fibers and display increased nerve growth factor-induced elongation and neurite formation in the presence of quercetin-loaded PVA fibers relative to substrates formed from only PEO-Col fibers or PEO-Col and PVA fibers without quercetin.

AB - Polymeric drug releasing systems have numerous applications for the treatment of chronic diseases and traumatic injuries. In this study, a simple, cost-effective, and scalable method for dry spinning of crosslinked polyvinyl alcohol (PVA) fibers is presented. This method utilizes an entangled solution of PVA to form liquid bridges that are drawn into rapidly drying fibers through extensional flow. The fibers are crosslinked by a one-pot reaction in which glyoxal is introduced to the PVA solution prior to contact drawing. Failure analysis of fiber formation is used to understand the interplay of polymer concentration, glyoxal concentration, and crosslinking time to identify appropriate formulations for the production of glyoxal-crosslinked PVA fibers. The small molecule quercetin (an anti-inflammatory plant flavonoid) can be added to the one-pot reaction and is shown to be incorporated into the fibers in a concentration-dependent manner. Upon rehydration in an aqueous medium, the glyoxal-crosslinked PVA fiber scaffolds retain their morphology and slowly degrade, as measured over the course of 10 days. As the scaffolds degrade, they release the loaded quercetin, reaching a cumulative release of 56 ± 6% of the loaded drug after 10 days. The bioactivity of the released quercetin is verified by combining quercetin-loaded fibers with contact-drawn polyethylene oxide-type I collagen (PEO-Col) fibers and monitoring the growth of PC12 cells on the fibers. PC12 cells readily attach to the PEO-Col fibers and display increased nerve growth factor-induced elongation and neurite formation in the presence of quercetin-loaded PVA fibers relative to substrates formed from only PEO-Col fibers or PEO-Col and PVA fibers without quercetin.

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Loading and Release of Quercetin from Contact-Drawn Polyvinyl Alcohol Fiber Scaffolds

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

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