Bordon, Gregor (2023). Next-generation lipidic drug delivery systems for osteoarthritis treatment. (Thesis). Universität Bern, Bern
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23bordon_g.pdf - Thesis Available under License Creative Commons: Attribution (CC-BY 4.0). Download (6MB) | Preview |
Abstract
Osteoarthritis (OA) is a prevalent degenerative joint disease, affecting over 500 million individuals globally and resulting in an economic burden exceeding $460 billion annually due to its increased incidence, attributed to factors like aging and obesity. Present therapeutic strategies are predominantly palliative, with a heavy reliance on corticosteroids and non-steroidal anti-inflammatory drugs, leaving disease modification unaddressed. Given the substantial shortcomings in current therapeutic paradigms, there is a pressing need for innovative, efficacious interventions. Intra-articular (IA) drug delivery systems (DDSs) are emerging as promising modalities due to their ability to directly target joint tissues, thereby maximizing therapeutic impact while minimizing systemic side effects. This thesis delineates the development of advanced lipid-based DDSs purposed for the optimized and sustained release of rapamycin (RAPA), focusing on enhanced joint retention, cartilage lubrication, and multifactorial targeting of OA pathophysiology. Chapter 2 conceptualizes a zinc-based liposomal DDS, specifically for localized OA therapy, to control RAPA release and achieve cartilage lubrication. Chapter 3 builds on this system and explores the potential of dendrimer-aggregated liposomes (DendriXALs) for IA OA therapy through exhaustive characterization and in vitro toxicity evaluations. Consecutively, Chapter 4 develops an injectable lipidic mesophase (LMP)-based DDS, prepared for on demand, enzyme-responsive RAPA release, exhibiting significant potential for sustained OA management. The developed lipidic DDSs represent an advanced and holistic alternative in OA therapeutic approaches. Through further in vivo validations of described concepts, they offer a potential to alleviate OA-induced disabilities and enhance the overall well-being of afflicted individuals.
| Item Type: | Thesis |
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| Dissertation Type: | Cumulative |
| Date of Defense: | 21 July 2023 |
| Subjects: | 500 Science > 540 Chemistry 500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
| Institute / Center: | 08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
| Depositing User: | Hammer Igor |
| Date Deposited: | 07 Jan 2025 09:54 |
| Last Modified: | 07 Jan 2025 23:25 |
| URI: | https://boristheses.unibe.ch/id/eprint/5718 |
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