{"id":{"repo_id":"ku","oai_identifier":"oai:kuscholarworks.ku.edu:1808/29847"},"canonical_url":"https://search.dev.ndltd.org/etd/ku/oai:kuscholarworks.ku.edu:1808/29847","repository":{"repo_id":"ku","name":"University of Kansas","base_url":"https://kuscholarworks.ku.edu/server/oai/request"},"display":{"title":"Development and biophysical characterization of a hyaluronic acid – vitamin E conjugate as a subcutaneous delivery platform","abstract":"The inherent properties of protein therapeutics (e.g. high molecular weight, charged, conformationally dependent) has historically limited their administration to parenteral routes which presents new challenges to their controlled delivery. Hydrogel and nanoparticle drug delivery systems can parenterally deliver a wide variety of drugs in a controlled manner while sustaining their therapeutic efficacy. Nanogels, formed from amphiphilic polymers, combine the unique and tunable properties of hydrogels and nanoparticles into one drug delivery system and have the potential to drastically improve the clinical applicability of protein therapeutics delivered subcutaneously. Hyaluronic acid, a ubiquitous polysaccharide of the extracellular matrix often used in drug delivery applications, was hydrophobically functionalized by the addition of glycine-modified vitamin E (-tocopherol) to form a self-assembling nanogel (HAtoco). The characterization of HAtoco was further developed by modifying its molecular weight and tocopherol substitution towards an optimum 33 kDa backbone with a 10mol% substitution. Physical and chemical characterization of the optimum HAtoco demonstrated its polydisperse effective size, stable colloidal and chemical stability and continued biodegradability by the endogenous enzyme hyaluronidase. In addition, HAtoco has shown the ability to double the in vitro release half-life of three model proteins (BSA, RNase, Lysozyme) and the in vivo release half-life of the clinical protein therapeutic Coversin when delivered subcutaneously to mice. Structural studies of HAtoco bound Coversin demonstrated destabilization of the protein upon adsorption, but released Coversin from the HAtoco nanogel demonstrated complement inhibition for at least 73 hours in vitro. Overall, HAtoco has demonstrated the ability to bind protein therapeutics in a reversible manner capable of prolonging their release in a therapeutically efficacious state.","abstract_html":"The inherent properties of protein therapeutics (e.g. high molecular weight, charged, conformationally dependent) has historically limited their administration to parenteral routes which presents new challenges to their controlled delivery. Hydrogel and nanoparticle drug delivery systems can parenterally deliver a wide variety of drugs in a controlled manner while sustaining their therapeutic efficacy. Nanogels, formed from amphiphilic polymers, combine the unique and tunable properties of hydrogels and nanoparticles into one drug delivery system and have the potential to drastically improve the clinical applicability of protein therapeutics delivered subcutaneously. Hyaluronic acid, a ubiquitous polysaccharide of the extracellular matrix often used in drug delivery applications, was hydrophobically functionalized by the addition of glycine-modified vitamin E (-tocopherol) to form a self-assembling nanogel (HAtoco). The characterization of HAtoco was further developed by modifying its molecular weight and tocopherol substitution towards an optimum 33 kDa backbone with a 10mol% substitution. Physical and chemical characterization of the optimum HAtoco demonstrated its polydisperse effective size, stable colloidal and chemical stability and continued biodegradability by the endogenous enzyme hyaluronidase. In addition, HAtoco has shown the ability to double the in vitro release half-life of three model proteins (BSA, RNase, Lysozyme) and the in vivo release half-life of the clinical protein therapeutic Coversin when delivered subcutaneously to mice. Structural studies of HAtoco bound Coversin demonstrated destabilization of the protein upon adsorption, but released Coversin from the HAtoco nanogel demonstrated complement inhibition for at least 73 hours in vitro. Overall, HAtoco has demonstrated the ability to bind protein therapeutics in a reversible manner capable of prolonging their release in a therapeutically efficacious state.","abstract_has_math":false,"creators":["Moulder, Kenneth Ryan"],"institution":"University of Kansas","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Forrest, Laird"],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-08-31","date_published":"2019-08-31","updated_at":"2026-07-24T02:46:17Z","subjects":["Pharmaceutical sciences","Coversin","Hyaluronic acid","Nanogel","Vitamin E"],"languages":["en"],"rights":["Copyright held by the author."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["http://dissertations.umi.com/ku:16765"],"render_values":[{"text":"http://dissertations.umi.com/ku:16765","href":"http://dissertations.umi.com/ku:16765","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/1808/29847","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Forrest, Laird"]},{"key":"dc:creator","label":"Author","values":["Moulder, Kenneth Ryan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2019-12-10T20:52:27Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2019-12-10T20:52:27Z"]},{"key":"dc:date.issued","label":"Date","values":["2019-08-31"]},{"key":"dc:publisher","label":"Institution","values":["University of Kansas"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Pharmaceutical sciences","Coversin","Hyaluronic acid","Nanogel","Vitamin E"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright held by the author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["http://dissertations.umi.com/ku:16765"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1808/29847"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The inherent properties of protein therapeutics (e.g. high molecular weight, charged, conformationally dependent) has historically limited their administration to parenteral routes which presents new challenges to their controlled delivery. Hydrogel and nanoparticle drug delivery systems can parenterally deliver a wide variety of drugs in a controlled manner while sustaining their therapeutic efficacy. Nanogels, formed from amphiphilic polymers, combine the unique and tunable properties of hydrogels and nanoparticles into one drug delivery system and have the potential to drastically improve the clinical applicability of protein therapeutics delivered subcutaneously. Hyaluronic acid, a ubiquitous polysaccharide of the extracellular matrix often used in drug delivery applications, was hydrophobically functionalized by the addition of glycine-modified vitamin E (-tocopherol) to form a self-assembling nanogel (HAtoco). The characterization of HAtoco was further developed by modifying its molecular weight and tocopherol substitution towards an optimum 33 kDa backbone with a 10mol% substitution. Physical and chemical characterization of the optimum HAtoco demonstrated its polydisperse effective size, stable colloidal and chemical stability and continued biodegradability by the endogenous enzyme hyaluronidase. In addition, HAtoco has shown the ability to double the in vitro release half-life of three model proteins (BSA, RNase, Lysozyme) and the in vivo release half-life of the clinical protein therapeutic Coversin when delivered subcutaneously to mice. Structural studies of HAtoco bound Coversin demonstrated destabilization of the protein upon adsorption, but released Coversin from the HAtoco nanogel demonstrated complement inhibition for at least 73 hours in vitro. Overall, HAtoco has demonstrated the ability to bind protein therapeutics in a reversible manner capable of prolonging their release in a therapeutically efficacious state."]},{"key":"dc:title","label":"Title","values":["Development and biophysical characterization of a hyaluronic acid – vitamin E conjugate as a subcutaneous delivery platform"]}]}],"canonical_facts":{"dc:contributor.advisor":["Forrest, Laird"],"dc:creator":["Moulder, Kenneth Ryan"],"dc:date.accessioned":["2019-12-10T20:52:27Z"],"dc:date.available":["2019-12-10T20:52:27Z"],"dc:date.issued":["2019-08-31"],"dc:description.abstract":["The inherent properties of protein therapeutics (e.g. high molecular weight, charged, conformationally dependent) has historically limited their administration to parenteral routes which presents new challenges to their controlled delivery. Hydrogel and nanoparticle drug delivery systems can parenterally deliver a wide variety of drugs in a controlled manner while sustaining their therapeutic efficacy. Nanogels, formed from amphiphilic polymers, combine the unique and tunable properties of hydrogels and nanoparticles into one drug delivery system and have the potential to drastically improve the clinical applicability of protein therapeutics delivered subcutaneously. Hyaluronic acid, a ubiquitous polysaccharide of the extracellular matrix often used in drug delivery applications, was hydrophobically functionalized by the addition of glycine-modified vitamin E (-tocopherol) to form a self-assembling nanogel (HAtoco). The characterization of HAtoco was further developed by modifying its molecular weight and tocopherol substitution towards an optimum 33 kDa backbone with a 10mol% substitution. Physical and chemical characterization of the optimum HAtoco demonstrated its polydisperse effective size, stable colloidal and chemical stability and continued biodegradability by the endogenous enzyme hyaluronidase. In addition, HAtoco has shown the ability to double the in vitro release half-life of three model proteins (BSA, RNase, Lysozyme) and the in vivo release half-life of the clinical protein therapeutic Coversin when delivered subcutaneously to mice. Structural studies of HAtoco bound Coversin demonstrated destabilization of the protein upon adsorption, but released Coversin from the HAtoco nanogel demonstrated complement inhibition for at least 73 hours in vitro. Overall, HAtoco has demonstrated the ability to bind protein therapeutics in a reversible manner capable of prolonging their release in a therapeutically efficacious state."],"dc:identifier.other":["http://dissertations.umi.com/ku:16765"],"dc:identifier.uri":["http://hdl.handle.net/1808/29847"],"dc:language.iso":["en"],"dc:publisher":["University of Kansas"],"dc:rights":["Copyright held by the author."],"dc:subject":["Pharmaceutical sciences","Coversin","Hyaluronic acid","Nanogel","Vitamin E"],"dc:title":["Development and biophysical characterization of a hyaluronic acid – vitamin E conjugate as a subcutaneous delivery platform"],"dc:type":["Dissertation"]},"updated_at":"2026-07-24T02:46:17Z"}