As a promising pH-triggerable molecular switch, trans -2-aminocyclohexanol (TACH) has a variety of applications. By introducing two hydrocarbon tails, multiple TACH-based lipids (flipids) have been designed and studied that are able to perform a drastic conformational flip upon protonation, loosening the stacking of hydrocarbon tails in lipid bilayers. Liposomes constructed from such flipids (fliposomes) can be disrupted by this acid-triggered conformational flip to cause a rapid release of a cargo specifically in areas of increased acidity (such as inflammation or ischemic tissues, solid tumor, and endosome pathway). A library of flipids has been built based on structural modifications of both amino headgroups and hydrophobic tails. A series of fliposomes have been constructed and their colloidal stability, capacity and pH-dependent leakage were investigated. A good correlation between the conformational switch of flipids studied by 1 H-NMR and the fliposomes' leakage indicated that the former is a cause for the latter. The obtained results showed that all the properties of fliposomes can be manipulated by selection of the amino headgroups structure and basicity, and the length and shape of hydrophobic tails, by using mixtures of different flipids or fliposomes, and by changing the content of flipids while constructing fliposomes. As a result, we prepared the pH-triggerable fliposomes with extraordinary characteristics: high stability in storage combined with instant release of their cargo in response to a weakly acidic medium. Fliposomes encapsulating the anticancer drug methotrexate (MTX) were applied to HeLa cells and demonstrated much higher cytotoxicity than the free drug and negative controls, indicating that they could conduct more efficient cellular delivery of MTX. The MTX-loaded fliposomes inhibited tumor growth in B16F1-melanoma-bearing nude mice compared to the control group, suggesting the anticancer activity of MTX delivered by pH-triggerable fliposomes in vivo. The results of research demonstrated the potential of fliposomes to serve as a viable drug delivery system.
","abstract_html":"<p>As a promising pH-triggerable molecular switch, trans -2-aminocyclohexanol (TACH) has a variety of applications. By introducing two hydrocarbon tails, multiple TACH-based lipids (flipids) have been designed and studied that are able to perform a drastic conformational flip upon protonation, loosening the stacking of hydrocarbon tails in lipid bilayers. Liposomes constructed from such flipids (fliposomes) can be disrupted by this acid-triggered conformational flip to cause a rapid release of a cargo specifically in areas of increased acidity (such as inflammation or ischemic tissues, solid tumor, and endosome pathway). A library of flipids has been built based on structural modifications of both amino headgroups and hydrophobic tails. A series of fliposomes have been constructed and their colloidal stability, capacity and pH-dependent leakage were investigated. A good correlation between the conformational switch of flipids studied by 1 H-NMR and the fliposomes' leakage indicated that the former is a cause for the latter. The obtained results showed that all the properties of fliposomes can be manipulated by selection of the amino headgroups structure and basicity, and the length and shape of hydrophobic tails, by using mixtures of different flipids or fliposomes, and by changing the content of flipids while constructing fliposomes. As a result, we prepared the pH-triggerable fliposomes with extraordinary characteristics: high stability in storage combined with instant release of their cargo in response to a weakly acidic medium. Fliposomes encapsulating the anticancer drug methotrexate (MTX) were applied to HeLa cells and demonstrated much higher cytotoxicity than the free drug and negative controls, indicating that they could conduct more efficient cellular delivery of MTX. The MTX-loaded fliposomes inhibited tumor growth in B16F1-melanoma-bearing nude mice compared to the control group, suggesting the anticancer activity of MTX delivered by pH-triggerable fliposomes in vivo. The results of research demonstrated the potential of fliposomes to serve as a viable drug delivery system.</p>","abstract_has_math":false,"creators":["Liu, Xin"],"institution":null,"degree_name":"Doctor of Philosophy (Ph.D.)","degree_level":"Dissertation - Pacific Access Restricted","degree_discipline":"Pharmaceutical and Chemical Sciences","degree_department":null,"school":null,"contributors":["Vyacheslav Sameshin"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-01-01T08:00:00Z","date_published":"2013-01-01T08:00:00Z","updated_at":"2026-07-24T05:36:00Z","subjects":["Organic chemistry","Pharmacy sciences","Pure sciences","Health and environmental sciences","Amphiphiles","Conformational switching","Controlled release","Fliposomes","Liposomes","Chemicals and Drugs","Chemistry","Medical Pharmacology","Medicinal-Pharmaceutical Chemistry","Medicine and Health Sciences","Pharmaceutical Preparations","Pharmacy and Pharmaceutical Sciences","Physical Sciences and Mathematics"],"languages":[],"rights":[],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["9781303533914"],"render_values":[{"text":"9781303533914","href":null,"code":true}]}]},"links":{"outbound_url":"https://scholarlycommons.pacific.edu/uop_etds/149","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Vyacheslav Sameshin"]},{"key":"dc:creator","label":"Author","values":["Liu, Xin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-06-29T08:55:12Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmaceutical and Chemical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation - Pacific Access Restricted"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (Ph.D.)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Organic chemistry","Pharmacy sciences","Pure sciences","Health and environmental sciences","Amphiphiles","Conformational switching","Controlled release","Fliposomes","Liposomes","Chemicals and Drugs","Chemistry","Medical Pharmacology","Medicinal-Pharmaceutical Chemistry","Medicine and Health Sciences","Pharmaceutical Preparations","Pharmacy and Pharmaceutical Sciences","Physical Sciences and Mathematics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["9781303533914","https://scholarlycommons.pacific.edu/uop_etds/149"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["As a promising pH-triggerable molecular switch, trans -2-aminocyclohexanol (TACH) has a variety of applications. By introducing two hydrocarbon tails, multiple TACH-based lipids (flipids) have been designed and studied that are able to perform a drastic conformational flip upon protonation, loosening the stacking of hydrocarbon tails in lipid bilayers. Liposomes constructed from such flipids (fliposomes) can be disrupted by this acid-triggered conformational flip to cause a rapid release of a cargo specifically in areas of increased acidity (such as inflammation or ischemic tissues, solid tumor, and endosome pathway). A library of flipids has been built based on structural modifications of both amino headgroups and hydrophobic tails. A series of fliposomes have been constructed and their colloidal stability, capacity and pH-dependent leakage were investigated. A good correlation between the conformational switch of flipids studied by 1 H-NMR and the fliposomes' leakage indicated that the former is a cause for the latter. The obtained results showed that all the properties of fliposomes can be manipulated by selection of the amino headgroups structure and basicity, and the length and shape of hydrophobic tails, by using mixtures of different flipids or fliposomes, and by changing the content of flipids while constructing fliposomes. As a result, we prepared the pH-triggerable fliposomes with extraordinary characteristics: high stability in storage combined with instant release of their cargo in response to a weakly acidic medium. Fliposomes encapsulating the anticancer drug methotrexate (MTX) were applied to HeLa cells and demonstrated much higher cytotoxicity than the free drug and negative controls, indicating that they could conduct more efficient cellular delivery of MTX. The MTX-loaded fliposomes inhibited tumor growth in B16F1-melanoma-bearing nude mice compared to the control group, suggesting the anticancer activity of MTX delivered by pH-triggerable fliposomes in vivo. The results of research demonstrated the potential of fliposomes to serve as a viable drug delivery system.
"]},{"key":"dc:source","label":"Dc Source","values":["291"]},{"key":"dc:title","label":"Title","values":["Fliposomes: pH-sensitive liposomes comprising novel trans-2-aminocyclohexanol-based amphiphiles as conformational switches for the liposome mebrane"]}]}],"canonical_facts":{"dc:contributor":["Vyacheslav Sameshin"],"dc:creator":["Liu, Xin"],"dc:date.available":["2018-06-29T08:55:12Z"],"dc:description.abstract":["As a promising pH-triggerable molecular switch, trans -2-aminocyclohexanol (TACH) has a variety of applications. By introducing two hydrocarbon tails, multiple TACH-based lipids (flipids) have been designed and studied that are able to perform a drastic conformational flip upon protonation, loosening the stacking of hydrocarbon tails in lipid bilayers. Liposomes constructed from such flipids (fliposomes) can be disrupted by this acid-triggered conformational flip to cause a rapid release of a cargo specifically in areas of increased acidity (such as inflammation or ischemic tissues, solid tumor, and endosome pathway). A library of flipids has been built based on structural modifications of both amino headgroups and hydrophobic tails. A series of fliposomes have been constructed and their colloidal stability, capacity and pH-dependent leakage were investigated. A good correlation between the conformational switch of flipids studied by 1 H-NMR and the fliposomes' leakage indicated that the former is a cause for the latter. The obtained results showed that all the properties of fliposomes can be manipulated by selection of the amino headgroups structure and basicity, and the length and shape of hydrophobic tails, by using mixtures of different flipids or fliposomes, and by changing the content of flipids while constructing fliposomes. As a result, we prepared the pH-triggerable fliposomes with extraordinary characteristics: high stability in storage combined with instant release of their cargo in response to a weakly acidic medium. Fliposomes encapsulating the anticancer drug methotrexate (MTX) were applied to HeLa cells and demonstrated much higher cytotoxicity than the free drug and negative controls, indicating that they could conduct more efficient cellular delivery of MTX. The MTX-loaded fliposomes inhibited tumor growth in B16F1-melanoma-bearing nude mice compared to the control group, suggesting the anticancer activity of MTX delivered by pH-triggerable fliposomes in vivo. The results of research demonstrated the potential of fliposomes to serve as a viable drug delivery system.
"],"dc:identifier":["9781303533914","https://scholarlycommons.pacific.edu/uop_etds/149"],"dc:rights":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:source":["291"],"dc:subject":["Organic chemistry","Pharmacy sciences","Pure sciences","Health and environmental sciences","Amphiphiles","Conformational switching","Controlled release","Fliposomes","Liposomes","Chemicals and Drugs","Chemistry","Medical Pharmacology","Medicinal-Pharmaceutical Chemistry","Medicine and Health Sciences","Pharmaceutical Preparations","Pharmacy and Pharmaceutical Sciences","Physical Sciences and Mathematics"],"dc:title":["Fliposomes: pH-sensitive liposomes comprising novel trans-2-aminocyclohexanol-based amphiphiles as conformational switches for the liposome mebrane"],"thesis:degree_discipline":["Pharmaceutical and Chemical Sciences"],"thesis:degree_level":["Dissertation - Pacific Access Restricted"],"thesis:degree_name":["Doctor of Philosophy (Ph.D.)"]},"updated_at":"2026-07-24T05:36:00Z"}