{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/78300"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/78300","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Gelatin nanoparticles for improved neuroprotection of intranasally delivered osteopontin in ischemic stroke","abstract":"Delivery of therapeutic agents to the brain is significantly hampered by the blood- brain barrier (BBB). Typically, only small, lipophilic molecules can freely enter the brain parenchyma following systemic administration. During the initial development phases, many drug candidates for neurological disorders are administered directly to target regions through use of cannula or intracranial injection. These administration routes are not practical clinically, and, as a result, many promising experimental drug candidates fail to enter clinical use due to an inability to effectively cross the BBB. The intranasal (IN) route is a promising pathway currently under investigation to bypass the BBB for rapid, non-invasive delivery of therapeutics to the brain. The advantages of the IN pathway are tempered by typically low efficiency, and, therefore, nanocarriers have been proposed to aid drug delivery to the brain following IN administration. Herein, we show the development of GNPs as a biodegradable, biocompatible, and cost-effective drug delivery platform using intranasal delivery of a peptide fragment to treat ischemic stroke in a rat model as proof-of-concept. Ischemic stroke is a leading cause of adult disability and 4th leading cause of death worldwide. The major impediments to functional recovery following stroke are short therapeutic windows and a lack of neuroprotective treatments. Current therapeutics emphasize reperfusion without further mechanisms to reduce infarct volume or promote healing and are most effective within 3 h of symptom onset: a window in which less than 30% of stroke victims receive medical attention. Osteopontin (OPN), a ubiquitous protein with roles in cell migration, inflammation, and apoptosis, has been shown to confer neuroprotection following ischemic stroke in animal models. In this work, we not only successfully fabricated GNPs with a uniform shape, but also demonstrated the ability of these GNPs to pass into the brain parenchyma following intranasal administration. Critically, the use of GNPs as a carrier allowed for a 71.57% reduction in mean infarct volume and extended the therapeutic window of intranasally administered OPN peptide to at least 6 h post-middle cerebral artery occlusion (MCAO). Our findings support the development of GNPs as a promising drug delivery platform for the intranasal treatment of ischemic stroke and, potentially, other neurologic disorders.","abstract_html":"Delivery of therapeutic agents to the brain is significantly hampered by the blood- brain barrier (BBB). Typically, only small, lipophilic molecules can freely enter the brain parenchyma following systemic administration. During the initial development phases, many drug candidates for neurological disorders are administered directly to target regions through use of cannula or intracranial injection. These administration routes are not practical clinically, and, as a result, many promising experimental drug candidates fail to enter clinical use due to an inability to effectively cross the BBB. The intranasal (IN) route is a promising pathway currently under investigation to bypass the BBB for rapid, non-invasive delivery of therapeutics to the brain. The advantages of the IN pathway are tempered by typically low efficiency, and, therefore, nanocarriers have been proposed to aid drug delivery to the brain following IN administration. Herein, we show the development of GNPs as a biodegradable, biocompatible, and cost-effective drug delivery platform using intranasal delivery of a peptide fragment to treat ischemic stroke in a rat model as proof-of-concept. Ischemic stroke is a leading cause of adult disability and 4th leading cause of death worldwide. The major impediments to functional recovery following stroke are short therapeutic windows and a lack of neuroprotective treatments. Current therapeutics emphasize reperfusion without further mechanisms to reduce infarct volume or promote healing and are most effective within 3 h of symptom onset: a window in which less than 30% of stroke victims receive medical attention. Osteopontin (OPN), a ubiquitous protein with roles in cell migration, inflammation, and apoptosis, has been shown to confer neuroprotection following ischemic stroke in animal models. In this work, we not only successfully fabricated GNPs with a uniform shape, but also demonstrated the ability of these GNPs to pass into the brain parenchyma following intranasal administration. Critically, the use of GNPs as a carrier allowed for a 71.57% reduction in mean infarct volume and extended the therapeutic window of intranasally administered OPN peptide to at least 6 h post-middle cerebral artery occlusion (MCAO). Our findings support the development of GNPs as a promising drug delivery platform for the intranasal treatment of ischemic stroke and, potentially, other neurologic disorders.","abstract_has_math":false,"creators":["Joachim, Elizabeth"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Bioengineering","degree_department":null,"school":null,"contributors":["Kim, Kyekyoon"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-07-22T22:15:41Z","date_published":"2015-07-22T22:15:41Z","updated_at":"2026-07-22T22:26:11Z","subjects":["Intranasal drug delivery","Gelatin nanoparticles","Neuroprotection","Ischemic stroke","Osteopontin"],"languages":[],"rights":["Copyright 2015 Elizabeth Joachim"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/78300","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kim, Kyekyoon"]},{"key":"dc:creator","label":"Author","values":["Joachim, Elizabeth"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-07-22T22:15:41Z","2015-05","2015-01-29","2015-5"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Bioengineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Intranasal drug delivery","Gelatin nanoparticles","Neuroprotection","Ischemic stroke","Osteopontin"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2015 Elizabeth Joachim"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/78300"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Delivery of therapeutic agents to the brain is significantly hampered by the blood- brain barrier (BBB). Typically, only small, lipophilic molecules can freely enter the brain parenchyma following systemic administration. During the initial development phases, many drug candidates for neurological disorders are administered directly to target regions through use of cannula or intracranial injection. These administration routes are not practical clinically, and, as a result, many promising experimental drug candidates fail to enter clinical use due to an inability to effectively cross the BBB. The intranasal (IN) route is a promising pathway currently under investigation to bypass the BBB for rapid, non-invasive delivery of therapeutics to the brain. The advantages of the IN pathway are tempered by typically low efficiency, and, therefore, nanocarriers have been proposed to aid drug delivery to the brain following IN administration. Herein, we show the development of GNPs as a biodegradable, biocompatible, and cost-effective drug delivery platform using intranasal delivery of a peptide fragment to treat ischemic stroke in a rat model as proof-of-concept. Ischemic stroke is a leading cause of adult disability and 4th leading cause of death worldwide. The major impediments to functional recovery following stroke are short therapeutic windows and a lack of neuroprotective treatments. Current therapeutics emphasize reperfusion without further mechanisms to reduce infarct volume or promote healing and are most effective within 3 h of symptom onset: a window in which less than 30% of stroke victims receive medical attention. Osteopontin (OPN), a ubiquitous protein with roles in cell migration, inflammation, and apoptosis, has been shown to confer neuroprotection following ischemic stroke in animal models. In this work, we not only successfully fabricated GNPs with a uniform shape, but also demonstrated the ability of these GNPs to pass into the brain parenchyma following intranasal administration. Critically, the use of GNPs as a carrier allowed for a 71.57% reduction in mean infarct volume and extended the therapeutic window of intranasally administered OPN peptide to at least 6 h post-middle cerebral artery occlusion (MCAO). Our findings support the development of GNPs as a promising drug delivery platform for the intranasal treatment of ischemic stroke and, potentially, other neurologic disorders.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2015-07-22 without embargo terms","The student, Elizabeth Joachim, accepted the attached license on 2015-01-23 at 12:09.","The student, Elizabeth Joachim, submitted this Thesis for approval on 2015-01-23 at 12:15.","This Thesis was approved for publication on 2015-01-29 at 16:38.","DSpace SAF Submission Ingestion Package generated from Vireo submission #7692 on 2015-07-22 at 10:29:39","Made available in DSpace on 2015-07-22T22:15:41Z (GMT). No. of bitstreams: 3 Joachim_Elizabeth1.pdf: 1504658 bytes, checksum: 21175daa2511e1f9c7d53cef2158544d (MD5) Joachim_Elizabeth.docx: 1441977 bytes, checksum: e0b31ac43b9d1111a33308b5778afc59 (MD5) license.txt: 4066 bytes, checksum: 36d7dcb59524d07be421efea71556498 (MD5) Previous issue date: 2015-01-29"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Gelatin nanoparticles for improved neuroprotection of intranasally delivered osteopontin in ischemic stroke"]}]}],"canonical_facts":{"dc:contributor":["Kim, Kyekyoon"],"dc:creator":["Joachim, Elizabeth"],"dc:date":["2015-07-22T22:15:41Z","2015-05","2015-01-29","2015-5"],"dc:description":["Delivery of therapeutic agents to the brain is significantly hampered by the blood- brain barrier (BBB). Typically, only small, lipophilic molecules can freely enter the brain parenchyma following systemic administration. During the initial development phases, many drug candidates for neurological disorders are administered directly to target regions through use of cannula or intracranial injection. These administration routes are not practical clinically, and, as a result, many promising experimental drug candidates fail to enter clinical use due to an inability to effectively cross the BBB. The intranasal (IN) route is a promising pathway currently under investigation to bypass the BBB for rapid, non-invasive delivery of therapeutics to the brain. The advantages of the IN pathway are tempered by typically low efficiency, and, therefore, nanocarriers have been proposed to aid drug delivery to the brain following IN administration. Herein, we show the development of GNPs as a biodegradable, biocompatible, and cost-effective drug delivery platform using intranasal delivery of a peptide fragment to treat ischemic stroke in a rat model as proof-of-concept. Ischemic stroke is a leading cause of adult disability and 4th leading cause of death worldwide. The major impediments to functional recovery following stroke are short therapeutic windows and a lack of neuroprotective treatments. Current therapeutics emphasize reperfusion without further mechanisms to reduce infarct volume or promote healing and are most effective within 3 h of symptom onset: a window in which less than 30% of stroke victims receive medical attention. Osteopontin (OPN), a ubiquitous protein with roles in cell migration, inflammation, and apoptosis, has been shown to confer neuroprotection following ischemic stroke in animal models. In this work, we not only successfully fabricated GNPs with a uniform shape, but also demonstrated the ability of these GNPs to pass into the brain parenchyma following intranasal administration. Critically, the use of GNPs as a carrier allowed for a 71.57% reduction in mean infarct volume and extended the therapeutic window of intranasally administered OPN peptide to at least 6 h post-middle cerebral artery occlusion (MCAO). Our findings support the development of GNPs as a promising drug delivery platform for the intranasal treatment of ischemic stroke and, potentially, other neurologic disorders.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2015-07-22 without embargo terms","The student, Elizabeth Joachim, accepted the attached license on 2015-01-23 at 12:09.","The student, Elizabeth Joachim, submitted this Thesis for approval on 2015-01-23 at 12:15.","This Thesis was approved for publication on 2015-01-29 at 16:38.","DSpace SAF Submission Ingestion Package generated from Vireo submission #7692 on 2015-07-22 at 10:29:39","Made available in DSpace on 2015-07-22T22:15:41Z (GMT). No. of bitstreams: 3 Joachim_Elizabeth1.pdf: 1504658 bytes, checksum: 21175daa2511e1f9c7d53cef2158544d (MD5) Joachim_Elizabeth.docx: 1441977 bytes, checksum: e0b31ac43b9d1111a33308b5778afc59 (MD5) license.txt: 4066 bytes, checksum: 36d7dcb59524d07be421efea71556498 (MD5) Previous issue date: 2015-01-29"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/78300"],"dc:rights":["Copyright 2015 Elizabeth Joachim"],"dc:subject":["Intranasal drug delivery","Gelatin nanoparticles","Neuroprotection","Ischemic stroke","Osteopontin"],"dc:title":["Gelatin nanoparticles for improved neuroprotection of intranasally delivered osteopontin in ischemic stroke"],"dc:type":["text"],"thesis:degree_discipline":["Bioengineering"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["M.S."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:11Z"}