Engineering targeted nanomedicines for advanced prostate cancer

• Κύριος συγγραφέας: Bahlool, Ahmad
• Άλλοι συγγραφείς: Κλεπετσάνης, Παύλος
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2020
• Θέματα: Prostate cancer; Nanomedicines; Liposomes; Nanoparticles; Targeted therapy; Καρκίνος προστάτη; Νανοϊατρική; Λιποσώματα; Νανοσωματίδια; Στοχευμένη θεραπεία

Prostate cancer is one of the most common types of cancer. Prostate cancer treatment protocols include the use of androgen deprivation therapy (ADT) and docetaxel which have high resistance rate in advanced disease stages. XD19 is a novel compound showed a promising activity on C4-2B prostate cancer cell lines and could be a key compound to overcome resistance due to its several mechanisms of action. XD19 was formulated into liposomes and poly(lactic-coglycolic acid) copolymer (PLGA) nanoparticles (NPs) to overcome solubility issue. The influence of different experimental parameters on the physicochemical properties and drug loading of XD19 in the liposomes and PLGA NPs were evaluated. In this study, our results demonstrate the significant effect of varying liposome composition and lipid:drug molar ratio on drug loading of XD19 in liposomes. We also investigated the effect of PLGA polymer type, drug to polymer ratio (w/w) and PEGylation on both the physicochemical properties and encapsulation efficiency of XD19 loaded PLGA NPs formulated using conventional bulk mixing nanoprecipitation. Then, a novel microfluidics-based device, a staggered herringbone micromixer (SHM), implemented for XD19 loaded PLGA NPs in order to upscale the formulation production for future in vivo use. In order to improve the formulation biodistribution, a prostate specific membrane antigen (PSMA) targeted liposomes were formulated and showed an increase uptake compared to non-targeted liposomes in PSMA expressing C4-2B cell line.