{"id":{"repo_id":"umkc","oai_identifier":"oai:mospace.umsystem.edu:10355/47466"},"canonical_url":"https://search.dev.ndltd.org/etd/umkc/oai:mospace.umsystem.edu:10355/47466","repository":{"repo_id":"umkc","name":"University of Missouri - Kansas City","base_url":"https://mospace.umsystem.edu/oai/request"},"display":{"title":"Development of polymeric nanoparticulate formulation encapsulating protein molecules following hydrophobic ion pairing complexation","abstract":"Several formulation strategies have been employed to enable sustained delivery of antibody therapeutics by nanoparticulate based dosage forms. However, development of sustained release nanoparticulate based dosage form for protein therapeutics represents a real challenge to scientists. These protein molecules are prone to denaturation under stress conditions such as sonication and presence of organic solvents. Another limiting factor in developing nanoparticulate formulation of protein therapeutics is their hydrophilic nature. Because of hydrophilic nature, these molecules partition poorly into polymer matrix leading to very low encapsulation efficiency. Hydrophobic ion pairing (HIP) complexation represents a novel approach to enhance protein encapsulation into nanoparticles. It also stabilizes protein molecules during nanoparticle preparation. We have chosen two model antibody proteins: Human IgG-Fab fragment and Human IgG, and prepared their HIP complexes. Different ion pairing agents and HIP complexation parameters were optimized. Consequently, optimized HIP complexes were loaded in polymeric nanoparticles. As a result, significant augmentation in encapsulation efficiency of these protein molecules was observed in the nanoparticles. Based on optimized parameters with IgG-Fab fragment, ranibizumab (Lucentis®), an anti-VEGF antibody fragment used for the treatment of age-related macular degeneration, loaded nanoparticulate formulation was also successfully developed. Developed nanoparticles formulations were characterized with respect to particle size, surface morphology and stability of entrapped protein. Further, nanoparticles were suspended in thermosensitive gel to achieve sustained release. HIP complexation has provided sustained release of protein from nanoparticles suspended in thermosensitive gel. Released protein maintained their physical stability and biological activity. No deleterious effects of HIP complexation and method of nanoparticles preparation on protein stability were observed.","abstract_html":"Several formulation strategies have been employed to enable sustained delivery of antibody therapeutics by nanoparticulate based dosage forms. However, development of sustained release nanoparticulate based dosage form for protein therapeutics represents a real challenge to scientists. These protein molecules are prone to denaturation under stress conditions such as sonication and presence of organic solvents. Another limiting factor in developing nanoparticulate formulation of protein therapeutics is their hydrophilic nature. Because of hydrophilic nature, these molecules partition poorly into polymer matrix leading to very low encapsulation efficiency. Hydrophobic ion pairing (HIP) complexation represents a novel approach to enhance protein encapsulation into nanoparticles. It also stabilizes protein molecules during nanoparticle preparation. We have chosen two model antibody proteins: Human IgG-Fab fragment and Human IgG, and prepared their HIP complexes. Different ion pairing agents and HIP complexation parameters were optimized. Consequently, optimized HIP complexes were loaded in polymeric nanoparticles. As a result, significant augmentation in encapsulation efficiency of these protein molecules was observed in the nanoparticles. Based on optimized parameters with IgG-Fab fragment, ranibizumab (Lucentis®), an anti-VEGF antibody fragment used for the treatment of age-related macular degeneration, loaded nanoparticulate formulation was also successfully developed. Developed nanoparticles formulations were characterized with respect to particle size, surface morphology and stability of entrapped protein. Further, nanoparticles were suspended in thermosensitive gel to achieve sustained release. HIP complexation has provided sustained release of protein from nanoparticles suspended in thermosensitive gel. Released protein maintained their physical stability and biological activity. No deleterious effects of HIP complexation and method of nanoparticles preparation on protein stability were observed.","abstract_has_math":false,"creators":["Patel, Ashaben"],"institution":"University of Missouri--Kansas City","degree_name":"Ph.D.","degree_level":"Doctoral","degree_discipline":"Pharmaceutical Sciences (UMKC)","degree_department":null,"school":null,"contributors":[],"advisors":["Mitra, Ashim K., 1954-"],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014","date_published":"2014","updated_at":"2026-07-24T05:16:57Z","subjects":[],"languages":["en_US"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10355/47466","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Mitra, Ashim K., 1954-"]},{"key":"dc:creator","label":"Author","values":["Patel, Ashaben"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-12-09T15:55:38Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2015-12-09T15:55:38Z"]},{"key":"dc:date.issued","label":"Date","values":["2014"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmaceutical Sciences (UMKC)","Chemistry (UMKC)"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Missouri--Kansas City"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10355/47466"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Title from PDF of title page, viewed on December 14, 2015","Dissertation advisor: Ashim K. Mitra","Vita","Includes bibliographical references (pages 178-190)","Thesis (Ph.D.)--School of Pharmacy and Department of Chemistry. University of Missouri--Kansas City, 2014"]},{"key":"dc:description.abstract","label":"Abstract","values":["Several formulation strategies have been employed to enable sustained delivery of antibody therapeutics by nanoparticulate based dosage forms. However, development of sustained release nanoparticulate based dosage form for protein therapeutics represents a real challenge to scientists. These protein molecules are prone to denaturation under stress conditions such as sonication and presence of organic solvents. Another limiting factor in developing nanoparticulate formulation of protein therapeutics is their hydrophilic nature. Because of hydrophilic nature, these molecules partition poorly into polymer matrix leading to very low encapsulation efficiency. Hydrophobic ion pairing (HIP) complexation represents a novel approach to enhance protein encapsulation into nanoparticles. It also stabilizes protein molecules during nanoparticle preparation. We have chosen two model antibody proteins: Human IgG-Fab fragment and Human IgG, and prepared their HIP complexes. Different ion pairing agents and HIP complexation parameters were optimized. Consequently, optimized HIP complexes were loaded in polymeric nanoparticles. As a result, significant augmentation in encapsulation efficiency of these protein molecules was observed in the nanoparticles. Based on optimized parameters with IgG-Fab fragment, ranibizumab (Lucentis®), an anti-VEGF antibody fragment used for the treatment of age-related macular degeneration, loaded nanoparticulate formulation was also successfully developed. Developed nanoparticles formulations were characterized with respect to particle size, surface morphology and stability of entrapped protein. Further, nanoparticles were suspended in thermosensitive gel to achieve sustained release. HIP complexation has provided sustained release of protein from nanoparticles suspended in thermosensitive gel. Released protein maintained their physical stability and biological activity. No deleterious effects of HIP complexation and method of nanoparticles preparation on protein stability were observed."]},{"key":"dc:title","label":"Title","values":["Development of polymeric nanoparticulate formulation encapsulating protein molecules following hydrophobic ion pairing complexation"]}]}],"canonical_facts":{"dc:contributor.advisor":["Mitra, Ashim K., 1954-"],"dc:creator":["Patel, Ashaben"],"dc:date.accessioned":["2015-12-09T15:55:38Z"],"dc:date.available":["2015-12-09T15:55:38Z"],"dc:date.issued":["2014"],"dc:description":["Title from PDF of title page, viewed on December 14, 2015","Dissertation advisor: Ashim K. Mitra","Vita","Includes bibliographical references (pages 178-190)","Thesis (Ph.D.)--School of Pharmacy and Department of Chemistry. University of Missouri--Kansas City, 2014"],"dc:description.abstract":["Several formulation strategies have been employed to enable sustained delivery of antibody therapeutics by nanoparticulate based dosage forms. However, development of sustained release nanoparticulate based dosage form for protein therapeutics represents a real challenge to scientists. These protein molecules are prone to denaturation under stress conditions such as sonication and presence of organic solvents. Another limiting factor in developing nanoparticulate formulation of protein therapeutics is their hydrophilic nature. Because of hydrophilic nature, these molecules partition poorly into polymer matrix leading to very low encapsulation efficiency. Hydrophobic ion pairing (HIP) complexation represents a novel approach to enhance protein encapsulation into nanoparticles. It also stabilizes protein molecules during nanoparticle preparation. We have chosen two model antibody proteins: Human IgG-Fab fragment and Human IgG, and prepared their HIP complexes. Different ion pairing agents and HIP complexation parameters were optimized. Consequently, optimized HIP complexes were loaded in polymeric nanoparticles. As a result, significant augmentation in encapsulation efficiency of these protein molecules was observed in the nanoparticles. Based on optimized parameters with IgG-Fab fragment, ranibizumab (Lucentis®), an anti-VEGF antibody fragment used for the treatment of age-related macular degeneration, loaded nanoparticulate formulation was also successfully developed. Developed nanoparticles formulations were characterized with respect to particle size, surface morphology and stability of entrapped protein. Further, nanoparticles were suspended in thermosensitive gel to achieve sustained release. HIP complexation has provided sustained release of protein from nanoparticles suspended in thermosensitive gel. Released protein maintained their physical stability and biological activity. No deleterious effects of HIP complexation and method of nanoparticles preparation on protein stability were observed."],"dc:identifier.uri":["https://hdl.handle.net/10355/47466"],"dc:language.iso":["en_US"],"dc:title":["Development of polymeric nanoparticulate formulation encapsulating protein molecules following hydrophobic ion pairing complexation"],"dc:type":["Thesis"],"thesis:degree_discipline":["Pharmaceutical Sciences (UMKC)","Chemistry (UMKC)"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Missouri--Kansas City"]},"updated_at":"2026-07-24T05:16:57Z"}