Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune Diseases
[eng] Autoimmune diseases are a diverse group of conditions where the immune system attacks the body's organs, affecting over 10% of the population, primarily women of working age. These diseases vary in severity and chronicity, often requiring tailored treatments involving immunosuppressive dr...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/215868 |
| Acceso en línea: | https://hdl.handle.net/2445/215868 http://hdl.handle.net/10803/692344 |
| Access Level: | acceso abierto |
| Palabra clave: | Immunologia Malalties autoimmunitàries Liposomes Administració de medicaments Immunology Autoimmune diseases Administration of drugs |
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Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune Diseases |
| title |
Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune Diseases |
| spellingShingle |
Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune Diseases Garrós Aristizábal, Núria Immunologia Malalties autoimmunitàries Liposomes Administració de medicaments Immunology Autoimmune diseases Administration of drugs |
| title_short |
Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune Diseases |
| title_full |
Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune Diseases |
| title_fullStr |
Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune Diseases |
| title_full_unstemmed |
Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune Diseases |
| title_sort |
Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune Diseases |
| dc.creator.none.fl_str_mv |
Garrós Aristizábal, Núria |
| author |
Garrós Aristizábal, Núria |
| author_facet |
Garrós Aristizábal, Núria |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Colom Codina, Helena Mallandrich Miret, Mireia Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació |
| dc.subject.none.fl_str_mv |
Immunologia Malalties autoimmunitàries Liposomes Administració de medicaments Immunology Autoimmune diseases Administration of drugs |
| topic |
Immunologia Malalties autoimmunitàries Liposomes Administració de medicaments Immunology Autoimmune diseases Administration of drugs |
| description |
[eng] Autoimmune diseases are a diverse group of conditions where the immune system attacks the body's organs, affecting over 10% of the population, primarily women of working age. These diseases vary in severity and chronicity, often requiring tailored treatments involving immunosuppressive drugs. Ongoing research to enhance treatment methods is crucial, focusing on drug administration, pharmacokinetics, adherence, and bioavailability. The thesis project aims to advance the treatment of autoimmune diseases, particularly focusing on liposomes as a formulation for an immunomodulatory drug, baricitinib. Liposomes are small vesicles made of phospholipids with biocompatible and biodegradable properties, suitable for encapsulating drugs with poor solubility. Baricitinib, the study drug, is an oral immunosuppressant effective in treating various conditions, including atopic dermatitis, rheumatoid arthritis, and COVID-19. However, its low water solubility poses a formulation challenge. The thesis project involves developing five different liposomes using the inverted evaporation method, tailored for topical and ophthalmological applications. Three liposomes are designed for atopic dermatitis (AD) treatment: Pure POPC liposomes – (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine) POPC:CHOL (0.8:0.2, mol/mol) liposomes – (1-palmitoyl-2-oleoyl-glycero-3- phosphocholine:Cholesterol) POPC:CHOL:CER (0.36:0.24:0.40, mol/mol/mol) liposomes – (1-palmitoyl-2- oleoyl-glycero-3-phosphocholine:Cholesterol:Ceramides) While two liposomes target Sjögren's Syndrome (SS): Pure Lα-PC liposomes POPE:POPG (3:1, mol/mol) liposomes – (1-palmitoyl-2-oleoyl- phosphatidylethanolamine: 1-Palmitoyl-2-oleoyl-sn-glycerol-3-phosphoglycerol) To achieve our objectives, we investigated the skin as a potential route for drug administration, both locally and systemically. Given the skin's protective barrier, drug diffusion is typically limited, necessitating the use of permeation enhancers; the impact of physical enhancers (solid titanium microneedles) and chemical enhancers on baricitinib permeation was explored. Two analytical HPLC methods were validated for baricitinib determination and quantification. And Confocal Raman Spectroscopy was used for the first time to obtain the baricitinib spectrum. Once we had identified the potential for percutaneous Baricitinib delivery as an alternative to oral administration, and we had validated two different methods for its detection and quantification, we began the studies with Baricitinib-loaded liposomes. The baricitinib-loaded liposomes for the treatment of SS were studied. The study proposes baricitinib-loaded ocular liposomal formulations, a novel approach for this condition. Two liposomal formulations, Lα-PC and POPE:POPG, were characterized for ocular administration. In vitro drug release, ex vivo permeation through ocular tissues, and tolerance assessments were conducted, showing no irritant effects on the ocular membrane. Both liposomes displayed suitable physicochemical properties for ocular use, and histological analysis revealed no structural changes. Our studies were finalized with the exploration of the use of liposomes for potential treatment of AD, a prevalent autoimmune skin condition. Physicochemical characterization, in vitro release studies, ex vivo permeation, and retention assessments on altered human skin were performed. The liposomes remained stable for at least a month and displayed promising properties. POPC:CHOL:CER liposome exhibited the highest permeation and skin retention, and no harmful or irritating effects were observed. This work indicates the potential of these liposomal formulations for AD treatment. In summary, thesis project focused on advancing autoimmune disease treatment, particularly using liposomes to deliver the immunomodulatory drug Baricitinib. The research explores various liposomal formulations for AD and SS, emphasizing the potential of percutaneous drug delivery and presenting promising results in terms of physicochemical properties, permeation profiles, and safety assessments. |
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2024 |
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2024 |
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info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion |
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https://hdl.handle.net/2445/215868 http://hdl.handle.net/10803/692344 |
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https://hdl.handle.net/2445/215868 http://hdl.handle.net/10803/692344 |
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Inglés |
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Inglés |
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cc by-nc-sa (c) Garrós Aristizábal, Núria, 2024 http://creativecommons.org/licenses/by-nc-sa/3.0/es/ info:eu-repo/semantics/openAccess |
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cc by-nc-sa (c) Garrós Aristizábal, Núria, 2024 http://creativecommons.org/licenses/by-nc-sa/3.0/es/ |
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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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Liposome Study of Baricitinib as a Novel Formula for Topical Treatment of Autoimmune DiseasesGarrós Aristizábal, NúriaImmunologiaMalalties autoimmunitàriesLiposomesAdministració de medicamentsImmunologyAutoimmune diseasesAdministration of drugs[eng] Autoimmune diseases are a diverse group of conditions where the immune system attacks the body's organs, affecting over 10% of the population, primarily women of working age. These diseases vary in severity and chronicity, often requiring tailored treatments involving immunosuppressive drugs. Ongoing research to enhance treatment methods is crucial, focusing on drug administration, pharmacokinetics, adherence, and bioavailability. The thesis project aims to advance the treatment of autoimmune diseases, particularly focusing on liposomes as a formulation for an immunomodulatory drug, baricitinib. Liposomes are small vesicles made of phospholipids with biocompatible and biodegradable properties, suitable for encapsulating drugs with poor solubility. Baricitinib, the study drug, is an oral immunosuppressant effective in treating various conditions, including atopic dermatitis, rheumatoid arthritis, and COVID-19. However, its low water solubility poses a formulation challenge. The thesis project involves developing five different liposomes using the inverted evaporation method, tailored for topical and ophthalmological applications. Three liposomes are designed for atopic dermatitis (AD) treatment: Pure POPC liposomes – (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine) POPC:CHOL (0.8:0.2, mol/mol) liposomes – (1-palmitoyl-2-oleoyl-glycero-3- phosphocholine:Cholesterol) POPC:CHOL:CER (0.36:0.24:0.40, mol/mol/mol) liposomes – (1-palmitoyl-2- oleoyl-glycero-3-phosphocholine:Cholesterol:Ceramides) While two liposomes target Sjögren's Syndrome (SS): Pure Lα-PC liposomes POPE:POPG (3:1, mol/mol) liposomes – (1-palmitoyl-2-oleoyl- phosphatidylethanolamine: 1-Palmitoyl-2-oleoyl-sn-glycerol-3-phosphoglycerol) To achieve our objectives, we investigated the skin as a potential route for drug administration, both locally and systemically. Given the skin's protective barrier, drug diffusion is typically limited, necessitating the use of permeation enhancers; the impact of physical enhancers (solid titanium microneedles) and chemical enhancers on baricitinib permeation was explored. Two analytical HPLC methods were validated for baricitinib determination and quantification. And Confocal Raman Spectroscopy was used for the first time to obtain the baricitinib spectrum. Once we had identified the potential for percutaneous Baricitinib delivery as an alternative to oral administration, and we had validated two different methods for its detection and quantification, we began the studies with Baricitinib-loaded liposomes. The baricitinib-loaded liposomes for the treatment of SS were studied. The study proposes baricitinib-loaded ocular liposomal formulations, a novel approach for this condition. Two liposomal formulations, Lα-PC and POPE:POPG, were characterized for ocular administration. In vitro drug release, ex vivo permeation through ocular tissues, and tolerance assessments were conducted, showing no irritant effects on the ocular membrane. Both liposomes displayed suitable physicochemical properties for ocular use, and histological analysis revealed no structural changes. Our studies were finalized with the exploration of the use of liposomes for potential treatment of AD, a prevalent autoimmune skin condition. Physicochemical characterization, in vitro release studies, ex vivo permeation, and retention assessments on altered human skin were performed. The liposomes remained stable for at least a month and displayed promising properties. POPC:CHOL:CER liposome exhibited the highest permeation and skin retention, and no harmful or irritating effects were observed. This work indicates the potential of these liposomal formulations for AD treatment. In summary, thesis project focused on advancing autoimmune disease treatment, particularly using liposomes to deliver the immunomodulatory drug Baricitinib. The research explores various liposomal formulations for AD and SS, emphasizing the potential of percutaneous drug delivery and presenting promising results in terms of physicochemical properties, permeation profiles, and safety assessments.[cat] Les malalties autoimmunes són un grup especial amb causa desconeguda en què el sistema immunitari es veu alterat i ataca òrgans del mateix individu. Algunes poden tenir afectació de pell i/o mucoses, sent aquestes les úniques dianes, o, per contra, a diferents òrgans a la vegada. Actualment, es coneixen més de 110 d'aquestes malalties i alguns estudis epidemiològics estimen que més del 10% de la població en pateix alguna. En general, el tractament consisteix a intentar reduir o minimitzar els seus efectes amb fàrmacs immunosupressors o immunomodulador. L'alta prevalença de malalties autoimmunes i l'impacte que tenen en la qualitat de vida dels pacients, fa necessària la investigació en aquesta àrea. És per això que el projecte de Tesi s'emmarca dins dels estudis biofarmacèutics i farmacocinètics d'un fàrmac immunomodulador. S'han elaborat un total de 5 liposomes diferents per mètode d'evaporació invertida o "micel·les invertides". Tres liposomes s'han estudiat per la seva aplicació tòpica enfocada en el tractament o coadjuvant d'aquest de la dermatitis atòpica i, els dos restants, s'han estudiat per la seva aplicació oftalmològica pel tractament o coadjuvant d'aquest del Síndrome de Sjögren. Tots 5 liposomes són vehicles del fàrmac baricitinib, un immunosupressor oral que inhibeix selectivament la janus quinasa 1 i 2 entre altres molècules, reduint signes i símptomes de malalties: la inflamació, l'activació cel·lular i la proliferació de cèl·lules immunes clau. Per aconseguir els nostres objectius primer es van validar dos mètodes analítics HPLC per a la determinació i quantificació de baricitinib, un HPLC-UV i un HPLC-fluorescència per a les mostres de concentració més baixa. Seguidament, vam estudiar la pell com a ruta d'administració del fàrmac usant diferents potenciadors de permeació. Un cop vam identificar el potencial de l'administració tòpica com una alternativa a l'administració oral, vam començar els estudis amb els liposomes en pell i mucosa.Universitat de BarcelonaColom Codina, HelenaMallandrich Miret, MireiaUniversitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació2024info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/215868http://hdl.handle.net/10803/692344Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentacióreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaIngléscc by-nc-sa (c) Garrós Aristizábal, Núria, 2024http://creativecommons.org/licenses/by-nc-sa/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2158682026-05-27T06:46:51Z |
| score |
15,812455 |