Development and Evaluation of Novel Baricitinib Formulation for Psoriasis Treatment
[eng] This doctoral thesis investigates the development of a lipid-based topical formulation of baricitinib for treating psoriasis, a chronic inflammatory skin condition. Psoriasis affects millions globally and presents with red, scaly patches on the skin. While oral baricitinib, a Janus kinase (JAK...
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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:2445/220514 |
| Acceso en línea: | https://hdl.handle.net/2445/220514 http://hdl.handle.net/10803/694275 |
| Access Level: | acceso abierto |
| Palabra clave: | Malalties de la pell Psoriasi Desenvolupament de medicaments Utilització de medicaments Skin diseases Psoriasis Drug development Drug utilization |
| Sumario: | [eng] This doctoral thesis investigates the development of a lipid-based topical formulation of baricitinib for treating psoriasis, a chronic inflammatory skin condition. Psoriasis affects millions globally and presents with red, scaly patches on the skin. While oral baricitinib, a Janus kinase (JAK) inhibitor, is used for autoimmune diseases like psoriasis, it can lead to systemic side effects. To address this, the research aims to create a topical formulation that targets affected skin, reducing systemic exposure and associated risks. The main objective of the study was to develop a topical formulation of baricitinib. The first phase involved assessing the solubility of baricitinib in different solvents and excipients, identifying those that would enhance skin permeability. The second phase focused on formulating and characterizing a stable topical product, evaluating its physical and chemical properties, and testing its efficacy and tolerability in a psoriasis model. Baricitinib showed poor solubility in water, a challenge for creating an effective topical treatment. However, the permeation enhancer Transcutol proved effective, increasing baricitinib’s solubility and penetration in skin tissues. This solvent allowed the drug to remain stable for at least a week, making it suitable for further formulation development. The lipid-based formulation (BCT-OS) was developed using excipients like Transcutol P, Labrafac Lipophile, and Lauroglycol 90 / Surfadone, chosen for their solubilizing and permeation-enhancing properties. The formulation was stable, had a skin-appropriate pH, and showed favorable rheological behavior for easy application. In vitro studies revealed that 80% of the drug was released from the formulation, while ex vivo permeation studies demonstrated that most of the drug remained in the skin, indicating potential for targeted treatment. The formulation’s efficacy was tested in an imiquimod-induced psoriasis model in mice. The results showed a significant reduction in common psoriasis symptoms, such as skin thickening, erythema, and edema. These findings confirmed baricitinib’s anti-inflammatory properties, facilitated by the inhibition of the JAK-STAT pathway, were effectively delivered through the topical formulation. The treatment also helped restore skin structure, alleviating symptoms. The formulation’s tolerability was confirmed through tests showing improved skin barrier function, with reduced transepidermal water loss and increased stratum corneum hydration. Histopathological analysis indicated no irritation or inflammation after application, confirming its safety for long-term use. The success of this formulation lies in the enhanced solubility of baricitinib achieved through the use of Transcutol. The lipid-based system enabled effective drug retention in the skin, limiting systemic exposure. In vivo studies further demonstrated the formulation’s therapeutic potential, significantly reducing psoriasis markers and restoring skin health. In summary, this research successfully developed a stable, effective, and well-tolerated topical formulation of baricitinib for psoriasis. The formulation’s localized action reduces the risks of systemic side effects, making it a promising candidate for future clinical studies. This innovation offers a new approach to treating psoriasis, improving patient outcomes and quality of life. |
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