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...
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| 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 |
| Sumario: | [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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