Design, formulation and characterization in vitro for theranostic nanobubbles

• Κύριος συγγραφέας: Rodrigues - Cabezas, Johanna - Gabriella
• Άλλοι συγγραφείς: Αντιμησιάρη, Σοφία
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2020
• Θέματα: Pancreatic cancer; Nanobubbles; Gemcitabine; Ultrasound; Καρκίνος παγκρέατος; Νανοφυσαλλίδες; Γεμσιταμπίνη; Υπέρηχοι

Pancreatic cancer has been considered as one of the biggest challenges of the 21st century with a survival rate of less than 5% in the following years after diagnosis. Diagnosis occurs at later stages because of the lack of accurate biomarkers. Causes of pancreatic ductal adenocarcinoma (PDA) are not clearly elucidated; nevertheless, family history, obesity, diabetes mellitus and pancreatitis are some factors that could contribute to the development of the disease. PDA has a unique tumour microenvironment (TME). It is a highly desmoplastic tumour with dense extracellular matrix (ECM), hypo-vascularisation, and a highly hypotoxic environment. Enhanced Permeation and Retention effect (EPR) may not be sufficient for pancreatic cancer treatment because of the uniquely barriers present in the TME. Gemcitabine is the current first-line treatment for pancreatic cancer; however, it has a poor chemical stability, short half-life, higher toxicity, and increased chemo-resistance. Nanobubbles (NBs) have been considered as the last generation of microbubbles (MBs). MBs and ultrasound are FDA-approved technologies, cost effective, and with high level of patient compliance. Nanobubble stability depends on Laplace pressure which is the ratio between the interfacial tension and the bubble radius. Synergistic effects of oxygen delivery and drug encapsulation in different compartments of dextran-shelled nanobubble structure (core, polymer shell and surfactant interface layer) were investigated to overcome current drawbacks with present treatment of pancreatic cancer. Polymer-based nanobubble formulations were characterised in-vitro and tested on cell lines.