Carone, Marianna (2023). Lipid-based drug delivery systems for inflammatory and fibrosis therapies. (Thesis). Universität Bern, Bern
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23carone_m_1_.pdf - Thesis Available under License Creative Commons: Attribution (CC-BY 4.0). Download (4MB) | Preview |
Abstract
Chronic inflammatory diseases pose a significant global health threat, contributing to over 50% of worldwide deaths. Prolonged inflammation often leads to fibrosis, a condition responsible for a substantial portion of mortality in the global north. Despite the high mortality rates, only two antifibrotic drugs are approved, emphasizing the urgent need for targeted therapeutic interventions. This dissertation presents a comprehensive exploration of drug delivery systems aimed at addressing inflammation and fibrosis, focusing on three distinct research units. The first unit introduces a gel platform, TIF-Gel, for the localized treatment of ulcerative colitis (UC). TIF-Gel utilizes rectal temperature-triggered formation, adhering to the colon wall, and releasing drugs in a sustained manner, demonstrating efficacy in reducing local inflammation. Preclinical studies have laid the foundation for a European patent, with potential applications in larger animal models to enhance clinical translation. The second unit addresses the scarcity of effective antifibrotic therapies, specifically targeting idiopathic pulmonary fibrosis. Investigational use of pirfenidone (PFD) across organs showed promise, leading to the development of ultra-high concentrated PFD-loaded liposomes and layer-by-layer (LbL) liposomal gels. Future research could explore underlying mechanisms enabling ultrahigh drug loading and validate the efficacy of the delivery system through in vivo fibrotic animal models. The third unit focuses on the development of a lipid-based oral dosage form for hepatic fibrosis. Utilizing 3D-printing, a printable lipid mesophase ink with a high percentage of pure lipid (S80) is developed, incorporating the water-insoluble drug obeticholic acid. The 3D-printed tablets exhibit promising characteristics, and further studies are suggested to bridge the gap between formulation development and in vivo effects. Collectively, these research units contribute to the advancement of drug delivery systems, offering promising strategies for the targeted treatment of chronic inflammatory diseases and fibrosis, potentially revolutionizing therapeutic approaches in the field.
| Item Type: | Thesis |
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| Dissertation Type: | Cumulative |
| Date of Defense: | 27 April 2023 |
| Subjects: | 500 Science > 540 Chemistry 500 Science > 570 Life sciences; biology |
| Institute / Center: | 08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
| Depositing User: | Hammer Igor |
| Date Deposited: | 20 Aug 2024 14:22 |
| Last Modified: | 21 Aug 2024 22:25 |
| URI: | https://boristheses.unibe.ch/id/eprint/5369 |
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