“Protein-liposome interactions: The impact of surface charge and fluidisation effect on protein binding”

Postgraduate Thesis uoadl:3221510 88 Read counter

Unit:
Κατεύθυνση Βιομηχανική Φαρμακευτική
Library of the School of Science
Deposit date:
2022-06-22
Year:
2022
Author:
Triantafyllopoulou Efstathia
Supervisors info:
Κωνσταντίνος Ν. Δεμέτζος, Καθηγητής, τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
« Μελέτη των αλληλεπιδράσεων λιποσωμάτων με πρωτεΐνες του αίματος: Ο ρόλος του φορτίου και της ρευστότητας της λιπιδικής διπλοστιβάδας στο σχηματισμό πρωτεϊνικής κορώνας»
Languages:
Greek
Translated title:
“Protein-liposome interactions: The impact of surface charge and fluidisation effect on protein binding”
Summary:
At the dawn of a new nanotechnological era in the pharmaceutical field, it is very important to examine and understand all the aspects that influence in vivo behaviour of nanoparticles. In this point of view, the interactions between serum proteins and liposomes with incorporated anionic, cationic, and/ or PEGylated lipids were investigated to elucidate the role of surface charge and bilayer fluidity in protein corona’s formation. 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), hydrogenated soybean phosphatidylcholine (HSPC), and 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC) liposomes with the presence or absence of 1,2-dipalmitoyl-sn-glycero-3-phospho-(1’-rac-glycerol) (sodium salt) (DPPG), 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (chloride salt) (DOTAP), and/or 1,2- dipalmitoylsn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DPPE-PEG 5000) lipids were prepared by the thin-film hydration method. The evaluation of their biophysical characteristics was enabled by differential scanning calorimetry and dynamic and electrophoretic light scattering. The physicochemical characteristics of mixed liposomes were compared before and after exposure to foetal bovine serum (FBS) and were correlated to calorimetric data. Our results indicate protein binding to all liposomal formulations. However, it is highlighted the importance of surface charge and fluidisation effect to the extent of protein adsorption. Additionally, considering the extensive use of cationic lipids for innovative delivery platforms, we deem PEGylation a key parameter, because even in a small proportion can reduce protein binding, and thus fast clearance and extreme toxicity without affecting positive charge. In conclusion, protein corona formation is a multifactorial issue, nevertheless fraction of stealthiness (Fs) could be a useful design parameter for fast screening of different formulations and quality prediction. Hopefully, this work will be used as a design road map for safe and effective drug and gene delivery.
Main subject category:
Science
Keywords:
differential scanning calorimetry (DSC); fetal bovine serum (FBS); cationic liposomes; anionic liposomes; opsonization
Index:
Yes
Number of index pages:
3
Contains images:
Yes
Number of references:
72
Number of pages:
81
File:
File access is restricted until 2025-07-19.

Τριανταφυλλοπούλου Ευσταθία - Διπλωματική Εργασία.pdf
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File access is restricted until 2025-07-19.