{"id":{"repo_id":"umkc","oai_identifier":"oai:mospace.umsystem.edu:10355/94462"},"canonical_url":"https://search.dev.ndltd.org/etd/umkc/oai:mospace.umsystem.edu:10355/94462","repository":{"repo_id":"umkc","name":"University of Missouri - Kansas City","base_url":"https://mospace.umsystem.edu/oai/request"},"display":{"title":"Protein and peptide-based biomaterials for treatment of COVID-19, crossing the blood-brain barrier and local delivery of antibiotics","abstract":"This dissertation has three major objectives. The first one is to discover novel peptide shuttles that can effectively transport different molecules across the Blood-Brain Barrier (BBB) and into the brain. Despite all the advancements in science and technology, discovering new shuttles that can effectively deliver drugs to the brain is challenging with a high failure rate. However, the discovery of a novel peptide capable of crossing the BBB would be a major breakthrough and could help deliver various therapeutics to the brain. Given the high-risk and high-reward nature of this project, I worked on a side project that is more straightforward. The objective of the second project is to develop a fibrin-thrombin hydrogel system that can release vancomycin over a sustained period of time to prevent implant-related infections. During the work on these two projects, the COVID-19 pandemic began to spread across the world, causing widespread disruption. Due to this, we decided to discover peptide drugs that could potentially be used as therapeutics to prevent the infection of COVID-19 virus. Therefore, the third objective of the dissertation is to discover anti-ACE2 peptides. In Chapter 1, we briefly discussed the COVID-19 virus and its infectivity. We then discussed the challenges of delivering therapeutics to the brain and the need to discover BBB penetrating peptides. We also briefly described the need to find ways to deliver antibiotics locally to prevent surgical site infections. The problem statement and objectives of the dissertation were also outlined in this chapter. In Chapter 2, we first reviewed the structure, mechanism of host infection, and various therapeutic strategies to combat the COVID-19 infection. Second, we discussed the challenges of drug transport to the brain, the various transport mechanisms, and how shuttle peptides can be used to deliver therapeutic cargos to the brain. Finally, we reviewed the mechanisms by which biofilm forms and how local application of antibiotics help prevent surgical site infections. In Chapter 3, we presented our work on the discovery of anti-ACE2 peptides that can block the interaction of ACE2 and the Spike protein present in COVID-19 virus. The binding of the Spike protein to the ACE2 receptor facilitates the entry of the virus into human cells, and blocking this interaction could be a potential treatment strategy for preventing infection caused by the COVID-19 virus. Using phage display, we discovered a 12 amino acid peptide (CSP4) that could block the interaction of ACE2 and the Spike protein, which was confirmed by blocking enzyme-linked immunoassay (ELISA) assay and Surface Plasmon Resonance (SPR) experiments. In addition, the blocking activity of the CSP4 peptide was enhanced by using a dimerization technique. Both CSP4 and CSP4 dimer showed increased specificity towards ACE2 and were nontoxic to cells. We concluded that CSP4 and CSP4 dimer could potentially be used as therapeutic or prophylactic agents against the COVID-19 virus. In Chapter 4, we described our efforts to discover BBB penetrating peptides. We optimized the screening method and used an appropriate dye to screen potential peptides. In addition, we repeated the fourth round of biopanning with modifications to facilitate the selection of candidates. We discovered one peptide (CAP-1) that showed higher specificity for crossing the BBB compared to other peptides. Further characterization of CAP-1 is required to confirm its ability to effectively cross the BBB. The CAP-1 peptide appears to be a promising candidate for use as a BBB shuttle. In chapter 5, we developed a fibrin-thrombin hydrogel delivery system encapsulating vancomycin that could release the antibiotic over a sustained period when applied to an implant surface, bone, or surgical wounds. Initially, free vancomycin was quickly released when entrapped into the fibrin-thrombin gel, not meeting our goal of sustained delivery. To address this issue, we prepared vancomycin nanoparticles using poly (lactic-co-glycolic acid) (PLGA) using a Design of Experiments (DOE) approach. We then entrapped the optimized nanoparticle formulation into the fibrin-thrombin gel and studied the release behavior of vancomycin. The entrapment of vancomycin nanoparticles helped prolong the release of vancomycin from the fibrin-thrombin hydrogel system. This strategy can be employed to prepare sustained release formulations for other drug molecules to maintain its local concentration.","abstract_html":"This dissertation has three major objectives. The first one is to discover novel peptide shuttles that can effectively transport different molecules across the Blood-Brain Barrier (BBB) and into the brain. Despite all the advancements in science and technology, discovering new shuttles that can effectively deliver drugs to the brain is challenging with a high failure rate. However, the discovery of a novel peptide capable of crossing the BBB would be a major breakthrough and could help deliver various therapeutics to the brain. Given the high-risk and high-reward nature of this project, I worked on a side project that is more straightforward. The objective of the second project is to develop a fibrin-thrombin hydrogel system that can release vancomycin over a sustained period of time to prevent implant-related infections. During the work on these two projects, the COVID-19 pandemic began to spread across the world, causing widespread disruption. Due to this, we decided to discover peptide drugs that could potentially be used as therapeutics to prevent the infection of COVID-19 virus. Therefore, the third objective of the dissertation is to discover anti-ACE2 peptides. In Chapter 1, we briefly discussed the COVID-19 virus and its infectivity. We then discussed the challenges of delivering therapeutics to the brain and the need to discover BBB penetrating peptides. We also briefly described the need to find ways to deliver antibiotics locally to prevent surgical site infections. The problem statement and objectives of the dissertation were also outlined in this chapter. In Chapter 2, we first reviewed the structure, mechanism of host infection, and various therapeutic strategies to combat the COVID-19 infection. Second, we discussed the challenges of drug transport to the brain, the various transport mechanisms, and how shuttle peptides can be used to deliver therapeutic cargos to the brain. Finally, we reviewed the mechanisms by which biofilm forms and how local application of antibiotics help prevent surgical site infections. In Chapter 3, we presented our work on the discovery of anti-ACE2 peptides that can block the interaction of ACE2 and the Spike protein present in COVID-19 virus. The binding of the Spike protein to the ACE2 receptor facilitates the entry of the virus into human cells, and blocking this interaction could be a potential treatment strategy for preventing infection caused by the COVID-19 virus. Using phage display, we discovered a 12 amino acid peptide (CSP4) that could block the interaction of ACE2 and the Spike protein, which was confirmed by blocking enzyme-linked immunoassay (ELISA) assay and Surface Plasmon Resonance (SPR) experiments. In addition, the blocking activity of the CSP4 peptide was enhanced by using a dimerization technique. Both CSP4 and CSP4 dimer showed increased specificity towards ACE2 and were nontoxic to cells. We concluded that CSP4 and CSP4 dimer could potentially be used as therapeutic or prophylactic agents against the COVID-19 virus. In Chapter 4, we described our efforts to discover BBB penetrating peptides. We optimized the screening method and used an appropriate dye to screen potential peptides. In addition, we repeated the fourth round of biopanning with modifications to facilitate the selection of candidates. We discovered one peptide (CAP-1) that showed higher specificity for crossing the BBB compared to other peptides. Further characterization of CAP-1 is required to confirm its ability to effectively cross the BBB. The CAP-1 peptide appears to be a promising candidate for use as a BBB shuttle. In chapter 5, we developed a fibrin-thrombin hydrogel delivery system encapsulating vancomycin that could release the antibiotic over a sustained period when applied to an implant surface, bone, or surgical wounds. Initially, free vancomycin was quickly released when entrapped into the fibrin-thrombin gel, not meeting our goal of sustained delivery. To address this issue, we prepared vancomycin nanoparticles using poly (lactic-co-glycolic acid) (PLGA) using a Design of Experiments (DOE) approach. We then entrapped the optimized nanoparticle formulation into the fibrin-thrombin gel and studied the release behavior of vancomycin. The entrapment of vancomycin nanoparticles helped prolong the release of vancomycin from the fibrin-thrombin hydrogel system. This strategy can be employed to prepare sustained release formulations for other drug molecules to maintain its local concentration.","abstract_has_math":false,"creators":["Adhikary, Pratik"],"institution":"University of Missouri--Kansas City","degree_name":"Ph.D. (Doctor of Philosophy)","degree_level":"Doctoral","degree_discipline":"Biomedical and Health Informatics (UMKC)","degree_department":null,"school":null,"contributors":[],"advisors":["Cheng, Kun (Professor)"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023","date_published":"2023","updated_at":"2026-07-24T05:19:28Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10355/94462","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Cheng, Kun (Professor)"]},{"key":"dc:creator","label":"Author","values":["Adhikary, Pratik"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2023-03-09T17:04:56Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2023-03-09T17:04:56Z"]},{"key":"dc:date.issued","label":"Date","values":["2023"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical and Health Informatics (UMKC)","Pharmaceutical Sciences (UMKC)"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D. (Doctor of Philosophy)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Missouri--Kansas City"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10355/94462"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Title from PDF of title page, viewed May 6, 2025","Dissertation advisor: Kun Cheng","Vita","Includes bibliographical references (pages 166-196)","Dissertation (Ph.D.)--Division of Pharmacology and Pharmaceutical Sciences, Department of Biomedical and Health Informatics. University of Missouri--Kansas City, 2023"]},{"key":"dc:description.abstract","label":"Abstract","values":["This dissertation has three major objectives. The first one is to discover novel peptide shuttles that can effectively transport different molecules across the Blood-Brain Barrier (BBB) and into the brain. Despite all the advancements in science and technology, discovering new shuttles that can effectively deliver drugs to the brain is challenging with a high failure rate. However, the discovery of a novel peptide capable of crossing the BBB would be a major breakthrough and could help deliver various therapeutics to the brain. Given the high-risk and high-reward nature of this project, I worked on a side project that is more straightforward. The objective of the second project is to develop a fibrin-thrombin hydrogel system that can release vancomycin over a sustained period of time to prevent implant-related infections. During the work on these two projects, the COVID-19 pandemic began to spread across the world, causing widespread disruption. Due to this, we decided to discover peptide drugs that could potentially be used as therapeutics to prevent the infection of COVID-19 virus. Therefore, the third objective of the dissertation is to discover anti-ACE2 peptides. In Chapter 1, we briefly discussed the COVID-19 virus and its infectivity. We then discussed the challenges of delivering therapeutics to the brain and the need to discover BBB penetrating peptides. We also briefly described the need to find ways to deliver antibiotics locally to prevent surgical site infections. The problem statement and objectives of the dissertation were also outlined in this chapter. In Chapter 2, we first reviewed the structure, mechanism of host infection, and various therapeutic strategies to combat the COVID-19 infection. Second, we discussed the challenges of drug transport to the brain, the various transport mechanisms, and how shuttle peptides can be used to deliver therapeutic cargos to the brain. Finally, we reviewed the mechanisms by which biofilm forms and how local application of antibiotics help prevent surgical site infections. In Chapter 3, we presented our work on the discovery of anti-ACE2 peptides that can block the interaction of ACE2 and the Spike protein present in COVID-19 virus. The binding of the Spike protein to the ACE2 receptor facilitates the entry of the virus into human cells, and blocking this interaction could be a potential treatment strategy for preventing infection caused by the COVID-19 virus. Using phage display, we discovered a 12 amino acid peptide (CSP4) that could block the interaction of ACE2 and the Spike protein, which was confirmed by blocking enzyme-linked immunoassay (ELISA) assay and Surface Plasmon Resonance (SPR) experiments. In addition, the blocking activity of the CSP4 peptide was enhanced by using a dimerization technique. Both CSP4 and CSP4 dimer showed increased specificity towards ACE2 and were nontoxic to cells. We concluded that CSP4 and CSP4 dimer could potentially be used as therapeutic or prophylactic agents against the COVID-19 virus. In Chapter 4, we described our efforts to discover BBB penetrating peptides. We optimized the screening method and used an appropriate dye to screen potential peptides. In addition, we repeated the fourth round of biopanning with modifications to facilitate the selection of candidates. We discovered one peptide (CAP-1) that showed higher specificity for crossing the BBB compared to other peptides. Further characterization of CAP-1 is required to confirm its ability to effectively cross the BBB. The CAP-1 peptide appears to be a promising candidate for use as a BBB shuttle. In chapter 5, we developed a fibrin-thrombin hydrogel delivery system encapsulating vancomycin that could release the antibiotic over a sustained period when applied to an implant surface, bone, or surgical wounds. Initially, free vancomycin was quickly released when entrapped into the fibrin-thrombin gel, not meeting our goal of sustained delivery. To address this issue, we prepared vancomycin nanoparticles using poly (lactic-co-glycolic acid) (PLGA) using a Design of Experiments (DOE) approach. We then entrapped the optimized nanoparticle formulation into the fibrin-thrombin gel and studied the release behavior of vancomycin. The entrapment of vancomycin nanoparticles helped prolong the release of vancomycin from the fibrin-thrombin hydrogel system. This strategy can be employed to prepare sustained release formulations for other drug molecules to maintain its local concentration."]},{"key":"dc:title","label":"Title","values":["Protein and peptide-based biomaterials for treatment of COVID-19, crossing the blood-brain barrier and local delivery of antibiotics"]}]}],"canonical_facts":{"dc:contributor.advisor":["Cheng, Kun (Professor)"],"dc:creator":["Adhikary, Pratik"],"dc:date.accessioned":["2023-03-09T17:04:56Z"],"dc:date.available":["2023-03-09T17:04:56Z"],"dc:date.issued":["2023"],"dc:description":["Title from PDF of title page, viewed May 6, 2025","Dissertation advisor: Kun Cheng","Vita","Includes bibliographical references (pages 166-196)","Dissertation (Ph.D.)--Division of Pharmacology and Pharmaceutical Sciences, Department of Biomedical and Health Informatics. University of Missouri--Kansas City, 2023"],"dc:description.abstract":["This dissertation has three major objectives. The first one is to discover novel peptide shuttles that can effectively transport different molecules across the Blood-Brain Barrier (BBB) and into the brain. Despite all the advancements in science and technology, discovering new shuttles that can effectively deliver drugs to the brain is challenging with a high failure rate. However, the discovery of a novel peptide capable of crossing the BBB would be a major breakthrough and could help deliver various therapeutics to the brain. Given the high-risk and high-reward nature of this project, I worked on a side project that is more straightforward. The objective of the second project is to develop a fibrin-thrombin hydrogel system that can release vancomycin over a sustained period of time to prevent implant-related infections. During the work on these two projects, the COVID-19 pandemic began to spread across the world, causing widespread disruption. Due to this, we decided to discover peptide drugs that could potentially be used as therapeutics to prevent the infection of COVID-19 virus. Therefore, the third objective of the dissertation is to discover anti-ACE2 peptides. In Chapter 1, we briefly discussed the COVID-19 virus and its infectivity. We then discussed the challenges of delivering therapeutics to the brain and the need to discover BBB penetrating peptides. We also briefly described the need to find ways to deliver antibiotics locally to prevent surgical site infections. The problem statement and objectives of the dissertation were also outlined in this chapter. In Chapter 2, we first reviewed the structure, mechanism of host infection, and various therapeutic strategies to combat the COVID-19 infection. Second, we discussed the challenges of drug transport to the brain, the various transport mechanisms, and how shuttle peptides can be used to deliver therapeutic cargos to the brain. Finally, we reviewed the mechanisms by which biofilm forms and how local application of antibiotics help prevent surgical site infections. In Chapter 3, we presented our work on the discovery of anti-ACE2 peptides that can block the interaction of ACE2 and the Spike protein present in COVID-19 virus. The binding of the Spike protein to the ACE2 receptor facilitates the entry of the virus into human cells, and blocking this interaction could be a potential treatment strategy for preventing infection caused by the COVID-19 virus. Using phage display, we discovered a 12 amino acid peptide (CSP4) that could block the interaction of ACE2 and the Spike protein, which was confirmed by blocking enzyme-linked immunoassay (ELISA) assay and Surface Plasmon Resonance (SPR) experiments. In addition, the blocking activity of the CSP4 peptide was enhanced by using a dimerization technique. Both CSP4 and CSP4 dimer showed increased specificity towards ACE2 and were nontoxic to cells. We concluded that CSP4 and CSP4 dimer could potentially be used as therapeutic or prophylactic agents against the COVID-19 virus. In Chapter 4, we described our efforts to discover BBB penetrating peptides. We optimized the screening method and used an appropriate dye to screen potential peptides. In addition, we repeated the fourth round of biopanning with modifications to facilitate the selection of candidates. We discovered one peptide (CAP-1) that showed higher specificity for crossing the BBB compared to other peptides. Further characterization of CAP-1 is required to confirm its ability to effectively cross the BBB. The CAP-1 peptide appears to be a promising candidate for use as a BBB shuttle. In chapter 5, we developed a fibrin-thrombin hydrogel delivery system encapsulating vancomycin that could release the antibiotic over a sustained period when applied to an implant surface, bone, or surgical wounds. Initially, free vancomycin was quickly released when entrapped into the fibrin-thrombin gel, not meeting our goal of sustained delivery. To address this issue, we prepared vancomycin nanoparticles using poly (lactic-co-glycolic acid) (PLGA) using a Design of Experiments (DOE) approach. We then entrapped the optimized nanoparticle formulation into the fibrin-thrombin gel and studied the release behavior of vancomycin. The entrapment of vancomycin nanoparticles helped prolong the release of vancomycin from the fibrin-thrombin hydrogel system. This strategy can be employed to prepare sustained release formulations for other drug molecules to maintain its local concentration."],"dc:identifier.uri":["https://hdl.handle.net/10355/94462"],"dc:title":["Protein and peptide-based biomaterials for treatment of COVID-19, crossing the blood-brain barrier and local delivery of antibiotics"],"thesis:degree_discipline":["Biomedical and Health Informatics (UMKC)","Pharmaceutical Sciences (UMKC)"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Ph.D. (Doctor of Philosophy)"],"thesis:institution_name":["University of Missouri--Kansas City"]},"updated_at":"2026-07-24T05:19:28Z"}