Targeted liposomal forms of a novel KRAS inhibitor for topical treatment of malignant pleural mesothelioma
| datacite.contributor.Supervisor | Αντιμησιάρη, Σοφία | |
| datacite.contributor.Supervisor | Μαραζιώτη, Αντωνία | |
| dc.contributor.author | Taressa, Korinan Fanta | |
| dc.contributor.other | Taressa, Korinan Fanta | |
| dc.date.accessioned | 2025-10-08T07:34:43Z | |
| dc.date.available | 2025-10-08T07:34:43Z | |
| dc.date.issued | 2025-07-09 | |
| dc.degree | masterThesis | |
| dc.description.abstract | Malignant pleural mesothelioma (MPM) is a fatal cancer with limited treatment options. Approximately half of the MPM cases contain KRAS mutations, including the KRAS G12C mutation. Due to the localized nature of MPM and extremely low solubilty and bioavailability of sotorasib, we developed liposomal formulations of sotorasib for local administration to reduce systemic exposure and increase efficacy. Liposomes were prepared via thin-film hydration method and active loading using ammonium sulfate gradient was used to improve sotorasib loading through pH gradient. Targeted liposomes were prepared by conjugating anti-CD146 mAb to PEG-maleimide. Liposomal formulations were characterized using DLS and HPLC for physicochemical characteristics and drug loading respectively. Active loading technique significantly improved drug loading efficiency compared to the passive method. Both the active and passive loaded liposomes maintained their physical stability during 30 days storage at 4℃. Liposomal formulations showed higher cytotoxicity and reduced colony formation compared to free sotorasib in LLC cell lines. Cellular uptake of both targeted and non-targeted (control) liposomes were low and lack targeting efficiency. In conclusion, this study showed enhanced sotorasib loading, short-term physical stability, and cell line specific in vitro efficacy. Future focus will be on further optimizing the formulation drug loading, targeting, in vivo therapeutic efficacy and safety evaluation. | |
| dc.identifier.uri | https://hdl.handle.net/10889/30491 | |
| dc.language.iso | en | |
| dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | |
| dc.subject | Malignant pleural mesothelioma (MPM) | |
| dc.subject | Targeted liposomes | |
| dc.subject | KRAS inhibitors | |
| dc.subject | Active drug loading | |
| dc.subject | Ant-CD146 mAb | |
| dc.subject.alternative | Στοχευμένα λιποσώματα | |
| dc.subject.alternative | Αναστολείς KRAS | |
| dc.title | Targeted liposomal forms of a novel KRAS inhibitor for topical treatment of malignant pleural mesothelioma | |
| dc.title.alternative | Στοχευμένες λιποσωμικές μορφές ενός νέου αναστολέα KRAS για τοπική θεραπεία κακοήθους μεσοθηλιώματος του υπεζωκότα |