Colloidal lipid gels: A novel approach to structure dispersions of lipids
[eng] Lipids are essential components in most living organisms whose functionality varies with their chemical structure. In an aqueous environment, diluted dispersions of phospholipids tend to form vesicles and other bilayered structures widely employed in the pharmaceutical field. These nanostructu...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/185517 |
| Acceso en línea: | https://hdl.handle.net/2445/185517 http://hdl.handle.net/10803/674231 |
| Access Level: | acceso abierto |
| Palabra clave: | Lípids Gels (Farmàcia) Membranes (Biologia) Col·loides Nanoestructures Lipids Gels (Pharmacy) Membranes (Biology) Colloids Nanostructures |
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España |
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Colloidal lipid gels: A novel approach to structure dispersions of lipids |
| title |
Colloidal lipid gels: A novel approach to structure dispersions of lipids |
| spellingShingle |
Colloidal lipid gels: A novel approach to structure dispersions of lipids Talló Domínguez, Kirian Lípids Gels (Farmàcia) Membranes (Biologia) Col·loides Nanoestructures Lipids Gels (Pharmacy) Membranes (Biology) Colloids Nanostructures |
| title_short |
Colloidal lipid gels: A novel approach to structure dispersions of lipids |
| title_full |
Colloidal lipid gels: A novel approach to structure dispersions of lipids |
| title_fullStr |
Colloidal lipid gels: A novel approach to structure dispersions of lipids |
| title_full_unstemmed |
Colloidal lipid gels: A novel approach to structure dispersions of lipids |
| title_sort |
Colloidal lipid gels: A novel approach to structure dispersions of lipids |
| dc.creator.none.fl_str_mv |
Talló Domínguez, Kirian |
| author |
Talló Domínguez, Kirian |
| author_facet |
Talló Domínguez, Kirian |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
López Serrano, Olga Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació |
| dc.subject.none.fl_str_mv |
Lípids Gels (Farmàcia) Membranes (Biologia) Col·loides Nanoestructures Lipids Gels (Pharmacy) Membranes (Biology) Colloids Nanostructures |
| topic |
Lípids Gels (Farmàcia) Membranes (Biologia) Col·loides Nanoestructures Lipids Gels (Pharmacy) Membranes (Biology) Colloids Nanostructures |
| description |
[eng] Lipids are essential components in most living organisms whose functionality varies with their chemical structure. In an aqueous environment, diluted dispersions of phospholipids tend to form vesicles and other bilayered structures widely employed in the pharmaceutical field. These nanostructures present excellent biocompatibility and work as drug delivery systems for poorly soluble drugs. Despite the remarkable properties of phospholipid nanostructures, those are mainly used in the liquid state; soft materials (with solid- like properties) tend to be made of other molecules, like polymers, able to form gels. The formation of phospholipid systems with a gel- like behaviour typically requires stabilising agents and increasing the phospholipids concentration above 40%. In these conditions, lipids can form cream-like dispersions of vesicles by mechanical procedures, or lyotropic phases by self-assembly. It has been reported that polymeric or clay colloidal systems can form diluted gels by using strategies to control particle aggregation into structured networks. Although diluted suspensions of lipid vesicles behave like a colloidal system, structured networks of vesicles leading to a gel have barely been described. This thesis aimed to develop an aqueous colloidal gel using a low concentration of lipids (mainly phospholipids) without requiring gelling agents. We started studying aqueous lipid systems composed of phospholipids (hydrogenated soy phosphatidylcholines) and oleic acid at different pH and molar ratios. These mixtures, ranging from 0.2% to 6% lipid concentration, resulted in suspensions of vesicles with a fluid behaviour. Results showed how particle size and membrane phase transition temperature decreased at high pH due to the ionisation of oleic acid. Further assays revealed that dispersions of phospholipids and fatty acids with a specific pH (5.5 – 7.5) could form structured gels. Gelation was achieved employing a temperature-induced procedure: After the hydration of the lipids, the resulting dispersion of vesicles was frozen at -20 ºC, heated above the main phase transition temperature, and cooled back to room temperature, where gelation was completed. These results were the first report of a colloidal gel formed exclusively by lipid membranes and vesicles in a high-water content (95%). The unique properties of such colloidal phospholipid/fatty acid gels granted this new type of system with the requirements of novelty and inventive step to be patented. Confocal microscopy illustrated that the microstructure of the gel was made of big vesicle aggregates connecting across the aqueous phase in a sponge-like matrix. The gel formation was attributed to the effect of charge in the lipid membranes. Rheological assays revealed that a lack of repulsion facilitated the rupture of the microstructure under deformation. In contrast, a high interparticle repulsion resulted in small, interconnected aggregates that deformed easier without yielding. This data led to a second patent, providing the details to form a broader range of gels stable in diverse conditions. Besides, we included preliminary experiments that tested the applicability of the gels for gastric application and as a topical system for permeation and wound healing. Finally, we assessed the distinct phases of the gelation mechanism through transmission electron microscopy, differential scanning calorimetry, and synchrotron X-ray scattering. These studies revealed a synergetic effect between freezing and heating that allows vesicles to fuse into tubular structures. The eventual cooling of the sample results in branched vesicle aggregates, finishing the formation of the gel. With this thesis, we have contributed to the development and study of a novel colloidal gel formed exclusively by lipids. The high water content and the phospholipid composition provide the gel with excellent biocompatibility. The ability to be formed with different lipids makes these gels a platform to design products with diverse pharmaceutical and biomedical applications. Future works should address a significant focus on their practical application. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion |
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doctoralThesis |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/185517 http://hdl.handle.net/10803/674231 |
| url |
https://hdl.handle.net/2445/185517 http://hdl.handle.net/10803/674231 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
(c) Talló Domínguez, Kirian, 2022 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) Talló Domínguez, Kirian, 2022 |
| eu_rights_str_mv |
openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Universitat de Barcelona |
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Universitat de Barcelona |
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Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentació reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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1869422315146575872 |
| spelling |
Colloidal lipid gels: A novel approach to structure dispersions of lipidsTalló Domínguez, KirianLípidsGels (Farmàcia)Membranes (Biologia)Col·loidesNanoestructuresLipidsGels (Pharmacy)Membranes (Biology)ColloidsNanostructures[eng] Lipids are essential components in most living organisms whose functionality varies with their chemical structure. In an aqueous environment, diluted dispersions of phospholipids tend to form vesicles and other bilayered structures widely employed in the pharmaceutical field. These nanostructures present excellent biocompatibility and work as drug delivery systems for poorly soluble drugs. Despite the remarkable properties of phospholipid nanostructures, those are mainly used in the liquid state; soft materials (with solid- like properties) tend to be made of other molecules, like polymers, able to form gels. The formation of phospholipid systems with a gel- like behaviour typically requires stabilising agents and increasing the phospholipids concentration above 40%. In these conditions, lipids can form cream-like dispersions of vesicles by mechanical procedures, or lyotropic phases by self-assembly. It has been reported that polymeric or clay colloidal systems can form diluted gels by using strategies to control particle aggregation into structured networks. Although diluted suspensions of lipid vesicles behave like a colloidal system, structured networks of vesicles leading to a gel have barely been described. This thesis aimed to develop an aqueous colloidal gel using a low concentration of lipids (mainly phospholipids) without requiring gelling agents. We started studying aqueous lipid systems composed of phospholipids (hydrogenated soy phosphatidylcholines) and oleic acid at different pH and molar ratios. These mixtures, ranging from 0.2% to 6% lipid concentration, resulted in suspensions of vesicles with a fluid behaviour. Results showed how particle size and membrane phase transition temperature decreased at high pH due to the ionisation of oleic acid. Further assays revealed that dispersions of phospholipids and fatty acids with a specific pH (5.5 – 7.5) could form structured gels. Gelation was achieved employing a temperature-induced procedure: After the hydration of the lipids, the resulting dispersion of vesicles was frozen at -20 ºC, heated above the main phase transition temperature, and cooled back to room temperature, where gelation was completed. These results were the first report of a colloidal gel formed exclusively by lipid membranes and vesicles in a high-water content (95%). The unique properties of such colloidal phospholipid/fatty acid gels granted this new type of system with the requirements of novelty and inventive step to be patented. Confocal microscopy illustrated that the microstructure of the gel was made of big vesicle aggregates connecting across the aqueous phase in a sponge-like matrix. The gel formation was attributed to the effect of charge in the lipid membranes. Rheological assays revealed that a lack of repulsion facilitated the rupture of the microstructure under deformation. In contrast, a high interparticle repulsion resulted in small, interconnected aggregates that deformed easier without yielding. This data led to a second patent, providing the details to form a broader range of gels stable in diverse conditions. Besides, we included preliminary experiments that tested the applicability of the gels for gastric application and as a topical system for permeation and wound healing. Finally, we assessed the distinct phases of the gelation mechanism through transmission electron microscopy, differential scanning calorimetry, and synchrotron X-ray scattering. These studies revealed a synergetic effect between freezing and heating that allows vesicles to fuse into tubular structures. The eventual cooling of the sample results in branched vesicle aggregates, finishing the formation of the gel. With this thesis, we have contributed to the development and study of a novel colloidal gel formed exclusively by lipids. The high water content and the phospholipid composition provide the gel with excellent biocompatibility. The ability to be formed with different lipids makes these gels a platform to design products with diverse pharmaceutical and biomedical applications. Future works should address a significant focus on their practical application.[cat] Els lípids són components essencials en la majoria d’organismes, i la funcionalitat varia segons la seva estructura química. Les dispersions aquoses de fosfolípids tendeixen a formar vesícules i altres estructures de bicapa que han estat àmpliament emprades en el camp farmacèutic. Aquestes nanoestructures presenten una excel·lent biocompatibilitat i funcionen com a sistemes d’administració de fàrmacs per a molècules poc solubles. Malgrat les excel·lents propietats d’aquestes nanoestructures lipídiques, el seu ús està principalment limitat en l’estat líquid. En canvi, els materials de tipus gel solen estar formats per altres molècules, com els polímers. La formació de sistemes lipídics amb un comportament tipus gel acostuma a requerir l’ús d’agents estabilitzants i incrementar la concentració per sobre el 40%. En aquestes condicions, els lípids poden formar dispersions viscoses de vesícules mitjançant processos mecànics o organitzar-se en fases cristall líquid. Aquesta tesi ha tingut com a objectiu desenvolupar un gel col·loidal emprant una baixa concentració de lípids (principalment fosfolípids) sense requerir agents gelificants. Duran els inicis d’aquesta tesi vam estudiar sistemes lipídics aquosos compostos de fosfolípids (fosfatidilcolines de soja hidrogenades) i àcid oleic a diferents relacions molars i de pH. Aquestes mescles, que van ser del 0,2% al 6% de concentració de lípids, van donar lloc a suspensions de vesícules amb un comportament fluid. Els resultats van mostrar com la mida de les partícules i la temperatura de transició de fase de membrana disminuïen a pH elevat a causa de la ionització de l'àcid oleic. Assajos posteriors van revelar que les dispersions de fosfolípids i àcids grassos amb un pH específic (entre 5,5 i 7,5) poden formar gels estructurats. La gelificació es va aconseguir mitjançant un procediment basat en canvis de temperatura: un cop hidratats els lípids, la dispersió resultant de vesícules es va congelar a -20 ºC, després es va escalfar per sobre de la temperatura de transició de fase i es va refredar fins a temperatura ambient, on es va completar la gelificació. Aquests, van ser els primers resultats d’un gel col·loidal format exclusivament per membranes lipídiques i vesícules amb un contingut elevat d’aigua (95%). Les propietats úniques d’aquests gels de fosfolípids i àcids grassos van atorgar a aquest nou tipus de sistema els requisits de novetat i activitat inventiva per poder ser patentats. Els resultats de microscòpia confocal van il·lustrar que la microestructura del gel estava formada per grans agregats de vesícules que connectaven entre ells a través de la fase aquosa. La formació del gel es va atribuir a l’efecte de la càrrega a les membranes lipídiques. Els assaigs reològics van revelar que la manca de repulsió facilitava la ruptura de la microestructura. En canvi, una alta repulsió entre partícules resultava en agregats petits i interconnectats que es deformaven més fàcilment sense ruptura. Aquestes dades van permetre una segona patent, que proporciona informació sobre una gamma més àmplia de gels estables en diverses condicions. A més, inclou experiments preliminars que van demostrar l’aplicabilitat dels gels a la pell com a agents per facilitar la permeabilitat o la cicatrització de ferides, i també per l’aplicació gàstrica. Finalment, vam avaluar les diferents fases del mecanisme de gelificació mitjançant microscòpia electrònica, calorimetria i dispersió de raigs X. Aquests estudis van revelar un efecte sinèrgic entre la congelació i el refredament que permeten la fusió de vesícules en estructures tubulars. L’eventual refredament de la mostra resulta en agregats de vesícules ramificades i la formació del gel. Aquesta tesi ha contribuït al desenvolupament i estudi d’un nou gel col·loidal format exclusivament per lípids. L’alt contingut d’aigua i la composició de fosfolípids proporcionen al gel una excel·lent biocompatibilitat. La capacitat de formar-se amb diferents lípids fan d’aquests gels una plataforma per dissenyar productes amb diverses aplicacions farmacèutiques i biomèdiques. Futurs projectes centrats en el seu ús pràctic podrien ser rellevants per trobar noves aplicacions.Universitat de BarcelonaLópez Serrano, OlgaUniversitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació2021info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/185517http://hdl.handle.net/10803/674231Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentacióreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Talló Domínguez, Kirian, 2022info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1855172026-05-27T06:46:51Z |
| score |
15,300719 |